To see the other types of publications on this topic, follow the link: Membrane neuronale.
Journal articles on the topic 'Membrane neuronale'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Membrane neuronale.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Simone, I. L., C. Tortorella, F. Federico, et al. "Contributo della risonanza magnetica spettroscopica del protone (1H-RMS) nella infezione da HIV." Rivista di Neuroradiologia 13, no. 1 (2000): 51–56. http://dx.doi.org/10.1177/197140090001300109.
Full textAbstract:
È stato condotto uno studio combinato di RMI e 1H-RMS (Magnetom Siemens 1,5 Tesla) in 60 pazienti sieropositivi per HIV (n. 25 encefalopatie-HIV correlate, n. 20 toxoplasmosi, n. 8 PML, n. 7 linfomi) e 22 controlli neurologici sieronegativi per HIV. Gli spettri sono stati acquisiti su volumi singoli localizzati su lesioni focali in toxoplasmosi, PML, linfomi o su lesioni diffuse nelle encefalopatie da HIV (sequenza Spin Echo, TE 135 ms). In tutti i sottogruppi HIV si è evidenziato un significativo decremento del rapporto NAA/Cr rispetto ai controlli neurologici, suggerendo un danno neuronale e/o assonale indipendentemente dall'eziologia. Tuttavia il rapporto NAA/Cr era più basso nelle PML e nei linfomi. Un significativo incremento del rapporto Cho/Cr era rilevato nelle encefalopatie da HIV, nelle PML e in particolare nei linfomi ove tale incremento era associato alla presenza del segnale dei lipidi, marker entrambi di un aumentato turnover e sintesi di membrane cellulari. Nelle PML si rilevava infine con elevata frequenza il segnale del lattato. I dati confermano una elevata sensibilità della 1H-RMS nel rilevare una compromissione metabolica cerebrale in corso di infezione da HIV. Nonostante una globale scarsa specificità nel discriminare lesioni di differente eziologia, determinati pattern metabolici possono risultare di supporto alla RMI per la diagnosi eziologica di alcune lesioni, per esempio di PML.
2
Martínez-Reyes, Harold, and Antonio Eblen-Zajjur. "Evaluación in silico del efecto de benzodiacepinas, ketamina y termo-dependencia sobre los patrones de descarga neuronal pre-Bötzinger de control respiratorio." Archivos de Neurociencias 23, no. 2 (2020): 25–35. http://dx.doi.org/10.31157/an.v23i2.8.
Full textAbstract:
Introducción: la fiebre y el uso de drogas como las benzodiacepinas (agonistas GABAA) y la ketamina (antagonista NMDA) se presentan con relativa frecuencia en anestesiología. La respiración es un patrón generado en el tallo cerebral, producto de una red compleja de centros ponto-medulares, que controlan las motoneuronas respiratorias gracias a la interacción de las neuronas inspiratorias del complejo pre-Bötzinger y las espiratorias del complejo Bötzinger. Estas neuronas poseen receptores de membrana del tipo GABAA y NMDA, que muestran alta termodependencia, sin embargo; se desconoce los cambios en el patrón de descarga neuronal inducidos por estas drogas y los cambios de temperatura corporal.
 Materiales y métodos: se generó un modelo validado de neurona Pre-inspiratoria (complejo pre-Bötzinger) incrementándose el peso sináptico gabaérgico equivalente al efecto de las benzodiacepinas o se redujo el peso sináptico NMDA equivalente al efecto de la ketamina en condiciones de hipo (35°C), normo (37°C) e hipertermia (40°C); cuantificándose el número y amplitud de las descargas neuronales. 
 Resultados: el aumento del peso sináptico GABAA o la reducción del de NMDA a temperaturas de 35°C, 37°C o 40°C redujo proporcionalmente el número de espigas y la amplitud del potencial de acción de la neurona Pre-I, mostrando curvas dosis-respuesta polinomiales de 2do. Orden, siendo las pendientes mayores a 35°C y a 40°C. 
 Conclusión: el efecto de benzodiacepinas o de ketamina a través de sus receptores GABAA y NMDA modifican in silico el patrón de descarga de la neurona Pre-I del núcleo Pre-Bötzinger, mostrando predominio del efecto gabaérgico y mayor termodependencia en las curvas dosis-respuesta en hipo e hipertermia lo que respalda el interés clínico de los datos.
3
Martínez-Reyes, Harold, and Antonio Eblen-Zajjur. "Evaluación in silico del efecto de benzodiacepinas, ketamina y termo-dependencia sobre los patrones de descarga neuronal pre-Bötzinger de control respiratorio." Archivos de Neurociencias 23, no. 2 (2020): 25–35. http://dx.doi.org/10.31157/archneurosciencesmex.v23i2.8.
Full textAbstract:
Introducción: la fiebre y el uso de drogas como las benzodiacepinas (agonistas GABAA) y la ketamina (antagonista NMDA) se presentan con relativa frecuencia en anestesiología. La respiración es un patrón generado en el tallo cerebral, producto de una red compleja de centros ponto-medulares, que controlan las motoneuronas respiratorias gracias a la interacción de las neuronas inspiratorias del complejo pre-Bötzinger y las espiratorias del complejo Bötzinger. Estas neuronas poseen receptores de membrana del tipo GABAA y NMDA, que muestran alta termodependencia, sin embargo; se desconoce los cambios en el patrón de descarga neuronal inducidos por estas drogas y los cambios de temperatura corporal.
 Materiales y métodos: se generó un modelo validado de neurona Pre-inspiratoria (complejo pre-Bötzinger) incrementándose el peso sináptico gabaérgico equivalente al efecto de las benzodiacepinas o se redujo el peso sináptico NMDA equivalente al efecto de la ketamina en condiciones de hipo (35°C), normo (37°C) e hipertermia (40°C); cuantificándose el número y amplitud de las descargas neuronales. 
 Resultados: el aumento del peso sináptico GABAA o la reducción del de NMDA a temperaturas de 35°C, 37°C o 40°C redujo proporcionalmente el número de espigas y la amplitud del potencial de acción de la neurona Pre-I, mostrando curvas dosis-respuesta polinomiales de 2do. Orden, siendo las pendientes mayores a 35°C y a 40°C. 
 Conclusión: el efecto de benzodiacepinas o de ketamina a través de sus receptores GABAA y NMDA modifican in silico el patrón de descarga de la neurona Pre-I del núcleo Pre-Bötzinger, mostrando predominio del efecto gabaérgico y mayor termodependencia en las curvas dosis-respuesta en hipo e hipertermia lo que respalda el interés clínico de los datos.
4
Morelli, Sabrina, Antonella Piscioneri, Enrico Drioli, and Loredana De Bartolo. "Neuronal Differentiation Modulated by Polymeric Membrane Properties." Cells Tissues Organs 204, no. 3-4 (2017): 164–78. http://dx.doi.org/10.1159/000477135.
Full textAbstract:
In this study, different collagen-blend membranes were successfully constructed by blending collagen with chitosan (CHT) or poly(lactic-co-glycolic acid) (PLGA) to enhance their properties and thus create new biofunctional materials with great potential use for neuronal tissue engineering and regeneration. Collagen blending strongly affected membrane properties in the following ways: (i) it improved the surface hydrophilicity of both pure CHT and PLGA membranes, (ii) it reduced the stiffness of CHT membranes, but (iii) it did not modify the good mechanical properties of PLGA membranes. Then, we investigated the effect of the different collagen concentrations on the neuronal behavior of the membranes developed. Morphological observations, immunocytochemistry, and morphometric measures demonstrated that the membranes developed, especially CHT/Col30, PLGA, and PLGA/Col1, provided suitable microenvironments for neuronal growth owing to their enhanced properties. The most consistent neuronal differentiation was obtained in neurons cultured on PLGA-based membranes, where a well-developed neuronal network was achieved due to their improved mechanical properties. Our findings suggest that tensile strength and elongation at break are key material parameters that have potential influence on both axonal elongation and neuronal structure and organization, which are of fundamental importance for the maintenance of efficient neuronal growth. Hence, our study has provided new insights regarding the effects of membrane mechanical properties on neuronal behavior, and thus it may help to design and improve novel instructive biomaterials for neuronal tissue engineering.
5
Dasgupta, Raktim, Markus S. Miettinen, Nico Fricke, Reinhard Lipowsky, and Rumiana Dimova. "The glycolipid GM1 reshapes asymmetric biomembranes and giant vesicles by curvature generation." Proceedings of the National Academy of Sciences 115, no. 22 (2018): 5756–61. http://dx.doi.org/10.1073/pnas.1722320115.
Full textAbstract:
The ganglioside GM1 is present in neuronal membranes at elevated concentrations with an asymmetric spatial distribution. It is known to generate curvature and can be expected to strongly influence the neuron morphology. To elucidate these effects, we prepared giant vesicles with GM1 predominantly present in one leaflet of the membrane, mimicking the asymmetric GM1 distribution in neuronal membranes. Based on pulling inward and outward tubes, we developed a technique that allowed the direct measurement of the membrane spontaneous curvature. Using vesicle electroporation and fluorescence intensity analysis, we were able to quantify the GM1 asymmetry across the membrane and to subsequently estimate the local curvature generated by the molecule in the bilayer. Molecular-dynamics simulations confirm the experimentally determined dependence of the membrane spontaneous curvature as a function of GM1 asymmetry. GM1 plays a crucial role in connection with receptor proteins. Our results on curvature generation of GM1 point to an additional important role of this ganglioside, namely in shaping neuronal membranes.
6
Nakada, C., Kenneth Ritchie, T. Fujiwara, et al. "LS3A1 Diffusion barrier in the neuronal cell membrane : a single molecule study." Seibutsu Butsuri 42, supplement2 (2002): S223. http://dx.doi.org/10.2142/biophys.42.s223_4.
Full text
7
SARRADIN, P., P. BERTHON, and F. LANTIER. "Le point sur l’épidémiologie et la physiopathologie des encéphalopathies spongiformes des ruminants." INRAE Productions Animales 10, no. 2 (1997): 123–32. http://dx.doi.org/10.20870/productions-animales.1997.10.2.3988.
Full textAbstract:
L’épidémie d’encéphalopathie spongiforme bovine (ESB) résulte de la consommation par les bovins de farines de viandes et d’os contaminées. En recyclant l’agent infectieux, ces farines ont permis d’amplifier la dissémination d’une maladie dont l’origine et l’agent responsable demeurent inconnus. Les hypothèses sur la nature protéique ou/et virale de l’agent sont évoquées, ainsi que l’éventualité d’une transmission à l’homme. Une grande partie de nos connaissances des encéphalopathies spongiformes résulte des études réalisées de longue date sur la tremblante des ovins. En particulier, l’idée que l’on peut se faire de la physiopathologie de l’infection des bovins est en grande partie extrapolée à partir du résultat d’infections expérimentales réalisées chez le mouton. Toutefois, la contamination des tissus lymphoïdes périphériques, qui est la règle au cours de la phase de dissémination dans l’organisme de l’agent de la tremblante, semble absente dans le cas de la maladie bovine. Il est donc possible que ce type de tissus, considéré comme infectieux en matière de tremblante, le soit peu au cours de la phase préclinique dans le cas de l’ESB. L’atteinte du système nerveux central des bovins pourrait alors résulter d’une dissémination empruntant les voies nerveuses.
 Les mécanismes conduisant à la mort neuronale responsable des symptômes observés restent mal connus. La protéine PrP, protéine normale de la membrane de nombreux types cellulaires, et qui s’accumule sous sa forme pathologique PrPSC au niveau des lésions est indispensable au processus pathologique. Son polymorphisme influence considérablement le devenir de l’infection, mais elle ne peut être tenue pour seule responsable de la transmission de la maladie.
8
Chen, Yuejun, Feifei Wang, Hui Long, Ying Chen, Ziyan Wu, and Lan Ma. "GRK5 promotes F-actin bundling and targets bundles to membrane structures to control neuronal morphogenesis." Journal of Cell Biology 194, no. 6 (2011): 905–20. http://dx.doi.org/10.1083/jcb.201104114.
Full textAbstract:
Neuronal morphogenesis requires extensive membrane remodeling and cytoskeleton dynamics. In this paper, we show that GRK5, a G protein–coupled receptor kinase, is critically involved in neurite outgrowth, dendrite branching, and spine morphogenesis through promotion of filopodial protrusion. Interestingly, GRK5 is not acting as a kinase but rather provides a key link between the plasma membrane and the actin cytoskeleton. GRK5 promoted filamentous actin (F-actin) bundling at the membranes of dynamic neuronal structures by interacting with both F-actin and phosphatidylinositol-4,5-bisphosphate. Moreover, separate domains of GRK5 mediated the coupling of actin cytoskeleton dynamics and membrane remodeling and were required for its effects on neuronal morphogenesis. Accordingly, GRK5 knockout mice exhibited immature spine morphology and deficient learning and memory. Our findings identify GRK5 as a critical mediator of dendritic development and suggest that coordinated actin cytoskeleton and membrane remodeling mediated by bifunctional actin-bundling and membrane-targeting molecules, such as GRK5, is crucial for proper neuronal morphogenesis and the establishment of functional neuronal circuitry.
9
Harrison, R., A. Jehanli, G. G. Lunt, and J. Rutter. "Autoantibodies to neuronal membranes in motor neurone disease." Journal of Neuroimmunology 16, no. 1 (1987): 71. http://dx.doi.org/10.1016/0165-5728(87)90238-4.
Full text
10
Sotnikov, Oleg S., Svetlana S. Sergeeva, and Tat'yana I. Vasyagina. "NEURONAL-GLIAL MEMBRANE CONTACTS DURING PESSIMAL ELECTRICAL STIMULATION." Morphological newsletter 28, no. 3 (2020): 35–50. http://dx.doi.org/10.20340/mv-mn.2020.28(3):35-50.
Full textAbstract:
After the creation of a method for obtaining inter-neuronal gap junctions in a nervous system devoid of glia, it is expedient to reproduce gap neuronal-glial contacts on a model that also contains hybrid neuronal-glial gap junctions, which, as you know, are functionally fundamentally different from inter-neuronal contacts. The experiments were carried out on the truncus sympathicus ganglia of laboratory rats using pessimal electrical stimulation and transmission electron microscopy. Electrical activation of ganglia with a frequency of up to 100 Hz revealed local and widespread variants of various neuronal-glial connections (contacts, bridges), fringed with peri-membrane filamentous proteins. They had a blurred veil that masked two-layer neuro-membranes. Some of the contacts resembled slit or dense 5-layer structures without a visible inter-neuronal slit, but with an extreme decrease in the thickness of the contact slit. The main result of the experiments was the formation, in addition to slotted, multiple septate (ladder) contacts. Relatively independent aggregates of the electron-dense substance of the septa were located inside the intercellular gaps, crossing both adjacent membranes, and, possibly, permeate of them. Near-membrane, poorly outlined pyramid-like protein cones associated with both cell membranes were also formed. Such membranes appeared to be dotted-dashed, that is, not continuous. A significant number of septic contact membranes had endocytic invaginations (invaginations) facing neuroplasm with pyramid-like marginal projections. All reactive altered structures that have arisen de novo are considered by the authors as developed under the influence of frequency electrical stimulation of denaturation and aggregation of intrinsic and perimembrane proteins.
11
Fatafta, Hebah, Mohammed Khaled, Michael C. Owen, Abdallah Sayyed-Ahmad та Birgit Strodel. "Amyloid-β peptide dimers undergo a random coil to β-sheet transition in the aqueous phase but not at the neuronal membrane". Proceedings of the National Academy of Sciences 118, № 39 (2021): e2106210118. http://dx.doi.org/10.1073/pnas.2106210118.
Full textAbstract:
Mounting evidence suggests that the neuronal cell membrane is the main site of oligomer-mediated neuronal toxicity of amyloid-β peptides in Alzheimer’s disease. To gain a detailed understanding of the mutual interference of amyloid-β oligomers and the neuronal membrane, we carried out microseconds of all-atom molecular dynamics (MD) simulations on the dimerization of amyloid-β (Aβ)42 in the aqueous phase and in the presence of a lipid bilayer mimicking the in vivo composition of neuronal membranes. The dimerization in solution is characterized by a random coil to β-sheet transition that seems on pathway to amyloid aggregation, while the interactions with the neuronal membrane decrease the order of the Aβ42 dimer by attenuating its propensity to form a β-sheet structure. The main lipid interaction partners of Aβ42 are the surface-exposed sugar groups of the gangliosides GM1. As the neurotoxic activity of amyloid oligomers increases with oligomer order, these results suggest that GM1 is neuroprotective against Aβ-mediated toxicity.
12
Kawahara, Masahiro, Isao Ohtsuka, Shoko Yokoyama, Midori Kato-Negishi та Yutaka Sadakane. "Membrane Incorporation, Channel Formation, and Disruption of Calcium Homeostasis by Alzheimer'sβ-Amyloid Protein". International Journal of Alzheimer's Disease 2011 (2011): 1–17. http://dx.doi.org/10.4061/2011/304583.
Full textAbstract:
Oligomerization, conformational changes, and the consequent neurodegeneration of Alzheimer'sβ-amyloid protein (AβP) play crucial roles in the pathogenesis of Alzheimer's disease (AD). Mounting evidence suggests that oligomeric AβPs cause the disruption of calcium homeostasis, eventually leading to neuronal death. We have demonstrated that oligomeric AβPs directly incorporate into neuronal membranes, form cation-sensitive ion channels (“amyloid channels”), and cause the disruption of calcium homeostasisviathe amyloid channels. Other disease-related amyloidogenic proteins, such as prion protein in prion diseases orα-synuclein in dementia with Lewy bodies, exhibit similarities in the incorporation into membranes and the formation of calcium-permeable channels. Here, based on our experimental results and those of numerous other studies, we review the current understanding of the direct binding of AβP into membrane surfaces and the formation of calcium-permeable channels. The implication of composition of membrane lipids and the possible development of new drugs by influencing membrane properties and attenuating amyloid channels for the treatment and prevention of AD is also discussed.
13
Ntarakas, Nikolaos, Inna Ermilova, and Alexander P. Lyubartsev. "Effect of lipid saturation on amyloid-beta peptide partitioning and aggregation in neuronal membranes: molecular dynamics simulations." European Biophysics Journal 48, no. 8 (2019): 813–24. http://dx.doi.org/10.1007/s00249-019-01407-x.
Full textAbstract:
Abstract Aggregation of amyloid-$$\beta $$β (Aβ) peptides, cleaved from the amyloid precursor protein, is known as a precursor of the Alzheimer’s disease (AD). It is also known that Alzheimer’s disease is characterized by a substantial decrease of the amount of polyunsaturated lipids in the neuronal membranes of the frontal gray matter. To get insight into possible interconnection of these phenomena, we have carried out molecular dynamics simulations of two fragments of A$$\beta $$β peptide, A$$\beta $$β$$_{1-28}$$1-28 and A$$\beta $$β$$_{26-40}$$26-40, in four different lipid bilayers: two monocomponent ones (14:0-14:0 PC, 18:0-22:6 PC), and two bilayers containing mixtures of 18:0-18:0 PE, 22:6-22:6 PE, 16:0-16:0 PC and 18:1-18:1 PC lipids of composition mimicking neuronal membranes in a “healthy” and “AD” brain. The simulations showed that the presence of lipids with highly unsaturated 22:6cis fatty acids chains strongly affects the interaction of amyloid-$$\beta $$β peptides with lipid membranes. The polyunsaturated lipids cause stronger adsorption of A$$\beta $$β-peptides by the membrane and lead to weaker binding between peptides when the latter form aggregates. This difference in the behaviour observed in monocomponent bilayers is propagated in a similar fashion to the mixed membranes mimicking composition of neuronal membranes in “healthy” and “AD” brains, with “healthy” membrane having higher fraction of polyunsaturated lipids. Our simulations give strong indication that it can be physical–chemical background of the interconnection between amyloid fibrillization causing Alzheimer’s disease, and content of polyunsaturated lipids in the neuronal membranes.
14
Tulodziecka, Karolina, Barbara B. Diaz-Rohrer, Madeline M. Farley, et al. "Remodeling of the postsynaptic plasma membrane during neural development." Molecular Biology of the Cell 27, no. 22 (2016): 3480–89. http://dx.doi.org/10.1091/mbc.e16-06-0420.
Full textAbstract:
Neuronal synapses are the fundamental units of neural signal transduction and must maintain exquisite signal fidelity while also accommodating the plasticity that underlies learning and development. To achieve these goals, the molecular composition and spatial organization of synaptic terminals must be tightly regulated; however, little is known about the regulation of lipid composition and organization in synaptic membranes. Here we quantify the comprehensive lipidome of rat synaptic membranes during postnatal development and observe dramatic developmental lipidomic remodeling during the first 60 postnatal days, including progressive accumulation of cholesterol, plasmalogens, and sphingolipids. Further analysis of membranes associated with isolated postsynaptic densities (PSDs) suggests the PSD-associated postsynaptic plasma membrane (PSD-PM) as one specific location of synaptic remodeling. We analyze the biophysical consequences of developmental remodeling in reconstituted synaptic membranes and observe remarkably stable microdomains, with the stability of domains increasing with developmental age. We rationalize the developmental accumulation of microdomain-forming lipids in synapses by proposing a mechanism by which palmitoylation of the immobilized scaffold protein PSD-95 nucleates domains at the postsynaptic plasma membrane. These results reveal developmental changes in lipid composition and palmitoylation that facilitate the formation of postsynaptic membrane microdomains, which may serve key roles in the function of the neuronal synapse.
15
Skene, J. H., and I. Virág. "Posttranslational membrane attachment and dynamic fatty acylation of a neuronal growth cone protein, GAP-43." Journal of Cell Biology 108, no. 2 (1989): 613–24. http://dx.doi.org/10.1083/jcb.108.2.613.
Full textAbstract:
Growth cones, the motile apparatus at the ends of elongating axons, are sites of extensive and dynamic membrane-cytoskeletal interaction and insertion of new membrane into the growing axon. One of the most abundant proteins in growth cone membranes is a protein designated GAP-43, whose synthesis increases dramatically in most neurons during periods of axon development or regeneration. We have begun to explore the role of GAP-43 in growth cone membrane functions by asking how the protein interacts with those membranes. Membrane-washing experiments indicate that mature GAP-43 is tightly bound to growth cone membranes, and partitioning of Triton X-114-solubilized GAP-43 between detergent-enriched and detergent-depleted phases indicates considerable hydrophobicity. The hydrophobic behavior of the protein is modulated by divalent cations, particularly zinc and calcium. In vivo labeling of GAP-43 in neonatal rat brain with [35S]methionine shows that GAP-43 is initially synthesized as a soluble protein that becomes attached to membranes posttranslationally. In tissue culture, both rat cerebral cortex cells and neuron-like PC12 cells actively incorporate [3H]palmitic acid into GAP-43. Isolated growth cones detached from their cell bodies also incorporate labeled fatty acid into GAP-43, suggesting active turnover of the fatty acid moieties on the mature protein. Hydrolysis of ester-like bonds with neutral hydroxylamine removes the bound fatty acid and exposes new thiol groups on GAP-43, suggesting that fatty acid is attached to the protein's only two cysteine residues, located in a short hydrophobic domain at the amino terminus. Modulation of the protein's hydrophobic behavior by divalent cations suggests that other domains, containing large numbers of negatively charged residues, might also contribute to GAP-43-membrane interactions. Our observations suggest a dynamic and reversible interaction of GAP-43 with growth cone membranes.
16
P. Eckert, Gunter. "Manipulation of Lipid Rafts in Neuronal Cells." Open Biology Journal 3, no. 1 (2010): 32–38. http://dx.doi.org/10.2174/18741967010030100032.
Full textAbstract:
Lipid rafts are specialized plasma membrane micro-domains highly enriched in cholesterol, sphingolipids and glycosylphosphatidylinositol (GPI) anchored proteins. Lipid rafts are thought to be located in the exofacial leaflet of plasma membranes. Functionally, lipid rafts are involved in intracellular trafficking of proteins and lipids, secretory and endocytotic pathways, signal transduction, inflammation and in cell-surface proteolysis. There has been substantial interest in lipid rafts in brain, both with respect to normal functioning and with certain neurodegenerative diseases. Based on the impact of lipid rafts on multitude biochemical pathways, modulation of lipid rafts is used to study related disease pathways and probably offers a target for pharmacological intervention. Lipid rafts can be targeted by modulation of its main components, namely cholesterol and sphingolipids. Other approaches include the modulation of membrane dynamics and it has been reported that protein-lipid interactions can vary the occurrence and composition of these membrane micro-domains. The present review summarizes the possibilities to modulate lipid rafts with focus on neuronal cells.
17
Kunduri, Govind, Daniel Turner-Evans, Yutaka Konya, et al. "Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants." Proceedings of the National Academy of Sciences 115, no. 38 (2018): E8919—E8928. http://dx.doi.org/10.1073/pnas.1808463115.
Full textAbstract:
Seizures induced by visual stimulation (photosensitive epilepsy; PSE) represent a common type of epilepsy in humans, but the molecular mechanisms and genetic drivers underlying PSE remain unknown, and no good genetic animal models have been identified as yet. Here, we show an animal model of PSE, in Drosophila, owing to defective cortex glia. The cortex glial membranes are severely compromised in ceramide phosphoethanolamine synthase (cpes)-null mutants and fail to encapsulate the neuronal cell bodies in the Drosophila neuronal cortex. Expression of human sphingomyelin synthase 1, which synthesizes the closely related ceramide phosphocholine (sphingomyelin), rescues the cortex glial abnormalities and PSE, underscoring the evolutionarily conserved role of these lipids in glial membranes. Further, we show the compromise in plasma membrane structure that underlies the glial cell membrane collapse in cpes mutants and leads to the PSE phenotype.
18
Hernandez, Martina L., Michael Marone, Karen M. Gorse, and Audrey D. Lafrenaye. "Cathepsin B Relocalization in Late Membrane Disrupted Neurons Following Diffuse Brain Injury in Rats." ASN Neuro 14 (January 2022): 175909142210991. http://dx.doi.org/10.1177/17590914221099112.
Full textAbstract:
Traumatic brain injury (TBI) has consequences that last for years following injury. While TBI can precipitate a variety of diffuse pathologies, the mechanisms involved in injury-induced neuronal membrane disruption remain elusive. The lysosomal cysteine protease, Cathepsin B (Cath B), and specifically its redistribution into the cytosol has been implicated in cell death. Little is known about Cath B or neuronal membrane disruption chronically following diffuse TBI. Therefore, the current study evaluated Cath B and diffuse neuronal membrane disruption over a more chronic post-injury window (6 h–4 w). We evaluated Cath B in adult male Sprague-Dawley rats following central fluid percussion injury (CFPI). Expression of Cath B, as well as Cath B-associated pro (Bak and AIF) and anti-apoptotic (Bcl-xl) proteins, were assessed using western blot analysis. Cath B activity was also assessed. Localization of Cath B was evaluated in the membrane disrupted and non-disrupted population following CFPI using immunohistochemistry paired with quantitative image analysis and ultrastructural verification. There was no difference in expression or activity of Cath B or any of the associated proteins between sham and CFPI at any time post-injury. Immunohistological studies, however, showed a sub-cellular re-localization of Cath B at 2 w and 4 w post-injury in the membrane disrupted neuronal population as compared to the time-point matched non-disrupted neurons. Both membrane disruption and Cath B relocalization appear linked to neuronal atrophy. These observations are indicative of a late secondary pathology that represents an opportunity for therapeutic treatment of these neurons following diffuse TBI. Summary Statement Lysosomal cathepsin B relocalizes to the cytosol in neurons with disrupted plasmalemmal membranes weeks following diffuse brain injury. Both the membrane disrupted and cathepsin B relocalized neuronal subpopulations displayed smaller soma and nucleus size compared to non-pathological neurons, indicating atrophy.
19
Abad-Rodriguez, Jose, Maria Dolores Ledesma, Katleen Craessaerts, et al. "Neuronal membrane cholesterol loss enhances amyloid peptide generation." Journal of Cell Biology 167, no. 5 (2004): 953–60. http://dx.doi.org/10.1083/jcb.200404149.
Full textAbstract:
Recent experimental and clinical retrospective studies support the view that reduction of brain cholesterol protects against Alzheimer's disease (AD). However, genetic and pharmacological evidence indicates that low brain cholesterol leads to neurodegeneration. This apparent contradiction prompted us to analyze the role of neuronal cholesterol in amyloid peptide generation in experimental systems that closely resemble physiological and pathological situations. We show that, in the hippocampus of control human and transgenic mice, only a small pool of endogenous APP and its β-secretase, BACE 1, are found in the same membrane environment. Much higher levels of BACE 1–APP colocalization is found in hippocampal membranes from AD patients or in rodent hippocampal neurons with a moderate reduction of membrane cholesterol. Their increased colocalization is associated with elevated production of amyloid peptide. These results suggest that loss of neuronal membrane cholesterol contributes to excessive amyloidogenesis in AD and pave the way for the identification of the cause of cholesterol loss and for the development of specific therapeutic strategies.
20
Yuyama, Kohei, Naoko Sekino-Suzuki, Yutaka Sanai, and Kohji Kasahara. "Signal Transduction of Neuronal Cell Adhesion Molecure TAG-1 via Lipid Rafts." MEMBRANE 30, no. 2 (2005): 91–93. http://dx.doi.org/10.5360/membrane.30.91.
Full text
21
Baksheeva, Viktoriia E., Ekaterina L. Nemashkalova, Alexander M. Firsov, et al. "Membrane Binding of Neuronal Calcium Sensor-1: Highly Specific Interaction with Phosphatidylinositol-3-Phosphate." Biomolecules 10, no. 2 (2020): 164. http://dx.doi.org/10.3390/biom10020164.
Full textAbstract:
Neuronal calcium sensors are a family of N-terminally myristoylated membrane-binding proteins possessing a different intracellular localization and thereby targeting unique signaling partner(s). Apart from the myristoyl group, the membrane attachment of these proteins may be modulated by their N-terminal positively charged residues responsible for specific recognition of the membrane components. Here, we examined the interaction of neuronal calcium sensor-1 (NCS-1) with natural membranes of different lipid composition as well as individual phospholipids in form of multilamellar liposomes or immobilized monolayers and characterized the role of myristoyl group and N-terminal lysine residues in membrane binding and phospholipid preference of the protein. NCS-1 binds to photoreceptor and hippocampal membranes in a Ca2+-independent manner and the binding is attenuated in the absence of myristoyl group. Meanwhile, the interaction with photoreceptor membranes is less dependent on myristoylation and more sensitive to replacement of K3, K7, and/or K9 of NCS-1 by glutamic acid, reflecting affinity of the protein to negatively charged phospholipids. Consistently, among the major phospholipids, NCS-1 preferentially interacts with phosphatidylserine and phosphatidylinositol with micromolar affinity and the interaction with the former is inhibited upon mutating of N-terminal lysines of the protein. Remarkably, NCS-1 demonstrates pronounced specific binding to phosphoinositides with high preference for phosphatidylinositol-3-phosphate. The binding does not depend on myristoylation and, unexpectedly, is not sensitive to the charge inversion mutations. Instead, phosphatidylinositol-3-phosphate can be recognized by a specific site located in the N-terminal region of the protein. These data provide important novel insights into the general mechanism of membrane binding of NCS-1 and its targeting to specific phospholipids ensuring involvement of the protein in phosphoinositide-regulated signaling pathways.
22
Liu, Tianshu, Pankaj Singh, James T. Jenkins, Anand Jagota, Maria Bykhovskaia, and Chung-Yuen Hui. "A continuum model of docking of synaptic vesicle to plasma membrane." Journal of The Royal Society Interface 12, no. 102 (2015): 20141119. http://dx.doi.org/10.1098/rsif.2014.1119.
Full textAbstract:
Neurotransmitter release from neuronal terminals is governed by synaptic vesicle fusion. Vesicles filled with transmitters are docked at the neuronal membrane by means of the SNARE machinery. After a series of events leading up to the fusion pore formation, neurotransmitters are released into the synaptic cleft. In this paper, we study the mechanics of the docking process. A continuum model is used to determine the deformation of a spherical vesicle and a plasma membrane, under the influence of SNARE-machinery forces and electrostatic repulsion. Our analysis provides information on the variation of in-plane stress in the membranes, which is known to affect fusion. Also, a simple model is proposed to study hemifusion.
23
Lang, T. "Imaging SNAREs at work in ‘unroofed’ cells – approaches that may be of general interest for functional studies on membrane proteins." Biochemical Society Transactions 31, no. 4 (2003): 861–64. http://dx.doi.org/10.1042/bst0310861.
Full textAbstract:
When cultured cells are subjected to a brief ultrasound pulse, their upper parts burst, but the basal plasma membranes with their embedded membrane–protein complexes remain intact. Such two-dimensional, paraformaldehyde-fixed plasma membrane sheets have been used in the past to visualize the morphology of the inner plasmalemmal leaflet by electron or light microscopy. More recently, fluorescence microscopy of unfixed native membranes has been applied to study SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) function. For instance, biochemical reactions of the plasmalemmal SNAREs with soluble fluorescent SNAREs, patching of SNARE and raft domains, and online monitoring of SNARE-mediated membrane fusion has been performed. The results obtained with the membrane sheet system have added some novel aspects to our understanding of the regulation of neuronal exocytosis. Surprisingly, SNAREs are concentrated in cholesterol-dependent microdomains that are different from membrane rafts. SNAREs in such domains are highly reactive, and define sites for vesicle exocytosis. Secretory granules that fuse on the membrane sheets are retrieved intact in a dynamin-dependent process, suggesting that the ‘kiss-and-run’ mechanism is not a reversed SNARE reaction, but is driven by a biochemically different mechanism. So far, studies of this type have focused on neuronal exocytosis; however, the method might be widely applicable. Data obtained with this system are derived from a 100% pure plasma membrane preparation that is only several seconds old, and membrane proteins are studied in their natural microenvironment that is defined by local lipid composition and putative bound proteins. Hence this approach yields results that most probably reflect the situation in a live cell.
24
Roorda, Robert D., Tobias M. Hohl, Ricardo Toledo-Crow, and Gero Miesenböck. "Video-Rate Nonlinear Microscopy of Neuronal Membrane Dynamics With Genetically Encoded Probes." Journal of Neurophysiology 92, no. 1 (2004): 609–21. http://dx.doi.org/10.1152/jn.00087.2004.
Full textAbstract:
Biological membranes decorated with suitable contrast agents give rise to nonlinear optical signals such as two-photon fluorescence and harmonic up-conversion when illuminated with ultra-short, high-intensity pulses of infrared laser light. Microscopic images based on these nonlinear contrasts were acquired at video or higher frame rates by scanning a focused illuminating spot rapidly across neural tissues. The scan engine relied on an acousto-optic deflector (AOD) to produce a fast horizontal raster and on corrective prisms to offset the AOD-induced dispersion of the ultra-short excitation light pulses in space and time. Two membrane-bound derivatives of the green fluorescent protein (GFP) were tested as nonlinear contrast agents. Synapto-pHluorin, a pH-sensitive GFP variant fused to a synaptic vesicle membrane protein, provided a time-resolved fluorescent read-out of neurotransmitter release at genetically specified synaptic terminals in the intact brain. Arrays of dually lipidated GFP molecules at the plasma membrane generated intense two-photon fluorescence but no detectable second-harmonic power. Comparison with second-harmonic generation by membranes stained with a synthetic styryl dye suggested that the genetically encoded chromophore arrangement lacked the orientational anisotropy and/or dipole density required for efficient coherent scattering of the incident optical field.
25
Cheng, Kwan H., Angela Graf, Amber Lewis, Thuong Pham, and Aakriti Acharya. "Exploring Membrane Binding Targets of Disordered Human Tau Aggregates on Lipid Rafts Using Multiscale Molecular Dynamics Simulations." Membranes 12, no. 11 (2022): 1098. http://dx.doi.org/10.3390/membranes12111098.
Full textAbstract:
The self-aggregation of tau, a microtubule-binding protein, has been linked to the onset of Alzheimer’s Disease. Recent studies indicate that the disordered tau aggregates, or oligomers, are more toxic than the ordered fibrils found in the intracellular neurofibrillary tangles of tau. At present, details of tau oligomer interactions with lipid rafts, a model of neuronal membranes, are not known. Using molecular dynamics simulations, the lipid-binding events, membrane-damage, and protein folding of tau oligomers on various lipid raft surfaces were investigated. Tau oligomers preferred to bind to the boundary domains (Lod) created by the coexisting liquid-ordered (Lo) and liquid-disordered (Ld) domains in the lipid rafts. Additionally, stronger binding of tau oligomers to the ganglioside (GM1) and phosphatidylserine (PS) domains, and subsequent protein-induced lipid chain order disruption and beta-sheet formation were detected. Our results suggest that GM1 and PS domains, located exclusively in the outer and inner leaflets, respectively, of the neuronal membranes, are specific membrane domain targets, whereas the Lod domains are non-specific targets, of tau oligomers binding to neurons. The molecular details of these specific and non-specific tau bindings to lipid rafts may provide new insights into understanding membrane-associated tauopathies leading to Alzheimer’s Disease.
26
Meitzen, John, Jessie I. Luoma, Marissa I. Boulware, et al. "Palmitoylation of Estrogen Receptors Is Essential for Neuronal Membrane Signaling." Endocrinology 154, no. 11 (2013): 4293–304. http://dx.doi.org/10.1210/en.2013-1172.
Full textAbstract:
In addition to activating nuclear estrogen receptor signaling, 17β-estradiol can also regulate neuronal function via surface membrane receptors. In various brain regions, these actions are mediated by the direct association of estrogen receptors (ERs) activating metabotropic glutamate receptors (mGluRs). These ER/mGluR signaling partners are organized into discrete functional microdomains via caveolin proteins. A central question that remains concerns the underlying mechanism by which these subpopulations of ERs are targeted to the surface membrane. One candidate mechanism is S-palmitoylation, a posttranscriptional modification that affects the subcellular distribution and function of the modified protein, including promoting localization to membranes. Here we test for the role of palmitoylation and the necessity of specific palmitoylacyltransferase proteins in neuronal membrane ER action. In hippocampal neurons, pharmacological inhibition of palmitoylation eliminated 17β-estradiol-mediated phosphorylation of cAMP response element-binding protein, a process dependent on surface membrane ERs. In addition, mutation of the palmitoylation site on estrogen receptor (ER) α blocks ERα-mediated cAMP response element-binding protein phosphorylation. Similar results were obtained after mutation of the palmitoylation site on ERβ. Importantly, mutation of either ERα or ERβ did not affect the ability of the reciprocal ER to signal at the membrane. In contrast, membrane ERα and ERβ signaling were both dependent on the expression of the palmitoylacyltransferase proteins DHHC-7 and DHHC-21. Neither mGluR activity nor caveolin or ER expression was affected by knockdown of DHHC-7 and DHHC-21. These data collectively suggest discrete mechanisms that regulate specific isoform or global membrane ER signaling in neurons separate from mGluR activity or nuclear ER function.
27
Wärmländer, Sebastian K. T. S., Nicklas Österlund, Cecilia Wallin та ін. "Metal binding to the amyloid-β peptides in the presence of biomembranes: potential mechanisms of cell toxicity". JBIC Journal of Biological Inorganic Chemistry 24, № 8 (2019): 1189–96. http://dx.doi.org/10.1007/s00775-019-01723-9.
Full textAbstract:
Abstract The amyloid-β (Aβ) peptides are key molecules in Alzheimer’s disease (AD) pathology. They interact with cellular membranes, and can bind metal ions outside the membrane. Certain oligomeric Aβ aggregates are known to induce membrane perturbations and the structure of these oligomers—and their membrane-perturbing effects—can be modulated by metal ion binding. If the bound metal ions are redox active, as e.g., Cu and Fe ions are, they will generate harmful reactive oxygen species (ROS) just outside the membrane surface. Thus, the membrane damage incurred by toxic Aβ oligomers is likely aggravated when redox-active metal ions are present. The combined interactions between Aβ oligomers, metal ions, and biomembranes may be responsible for at least some of the neuronal death in AD patients.
28
Xu, Yan, Victor E. Yushmanov, and Pei Tang. "NMR Studies of Drug Interaction with Membranes and Membrane-Associated Proteins." Bioscience Reports 22, no. 2 (2002): 175–96. http://dx.doi.org/10.1023/a:1020182404940.
Full textAbstract:
This review focuses on the recent developments in the study of drug interactions with biological membranes and membrane-associated proteins using nuclear magnetic resonance (NMR) spectroscopy and other spectroscopic techniques. Emphasis is placed on a class of low-affinity neurological agents as exemplified by volatile general anesthetics and structurally related compounds. The technical aspects are reviewed of how to prepare membrane-mimetic systems and of NMR approaches that are either in current use or opening new prospects. A brief literature survey covers studies ranging from drug distribution in simplified lipid matrix to specific drug interaction with neuronal receptors reconstituted in complicated synthetic membrane systems.
29
Angelova, Plamena R., Minee L. Choi, Alexey V. Berezhnov, et al. "Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation." Cell Death & Differentiation 27, no. 10 (2020): 2781–96. http://dx.doi.org/10.1038/s41418-020-0542-z.
Full textAbstract:
Abstract Protein aggregation and abnormal lipid homeostasis are both implicated in neurodegeneration through unknown mechanisms. Here we demonstrate that aggregate-membrane interaction is critical to induce a form of cell death called ferroptosis. Importantly, the aggregate-membrane interaction that drives ferroptosis depends both on the conformational structure of the aggregate, as well as the oxidation state of the lipid membrane. We generated human stem cell-derived models of synucleinopathy, characterized by the intracellular formation of α-synuclein aggregates that bind to membranes. In human iPSC-derived neurons with SNCA triplication, physiological concentrations of glutamate and dopamine induce abnormal calcium signaling owing to the incorporation of excess α-synuclein oligomers into membranes, leading to altered membrane conductance and abnormal calcium influx. α-synuclein oligomers further induce lipid peroxidation. Targeted inhibition of lipid peroxidation prevents the aggregate-membrane interaction, abolishes aberrant calcium fluxes, and restores physiological calcium signaling. Inhibition of lipid peroxidation, and reduction of iron-dependent accumulation of free radicals, further prevents oligomer-induced toxicity in human neurons. In summary, we report that peroxidation of polyunsaturated fatty acids underlies the incorporation of β-sheet-rich aggregates into the membranes, and that additionally induces neuronal death. This suggests a role for ferroptosis in Parkinson’s disease, and highlights a new mechanism by which lipid peroxidation causes cell death.
30
Becalska, Agata N., Charlotte F. Kelley, Cristina Berciu, et al. "Formation of membrane ridges and scallops by the F-BAR protein Nervous Wreck." Molecular Biology of the Cell 24, no. 15 (2013): 2406–18. http://dx.doi.org/10.1091/mbc.e13-05-0271.
Full textAbstract:
Eukaryotic cells are defined by extensive intracellular compartmentalization, which requires dynamic membrane remodeling. FER/Cip4 homology-Bin/amphiphysin/Rvs (F-BAR) domain family proteins form crescent-shaped dimers, which can bend membranes into buds and tubules of defined geometry and lipid composition. However, these proteins exhibit an unexplained wide diversity of membrane-deforming activities in vitro and functions in vivo. We find that the F-BAR domain of the neuronal protein Nervous Wreck (Nwk) has a novel higher-order structure and membrane-deforming activity that distinguishes it from previously described F-BAR proteins. The Nwk F-BAR domain assembles into zigzags, creating ridges and periodic scallops on membranes in vitro. This activity depends on structural determinants at the tips of the F-BAR dimer and on electrostatic interactions of the membrane with the F-BAR concave surface. In cells, Nwk-induced scallops can be extended by cytoskeletal forces to produce protrusions at the plasma membrane. Our results define a new F-BAR membrane-deforming activity and illustrate a molecular mechanism by which positively curved F-BAR domains can produce a variety of membrane curvatures. These findings expand the repertoire of F-BAR domain mediated membrane deformation and suggest that unique modes of higher-order assembly can define how these proteins sculpt the membrane.
31
Gong, Jihong, Ying Lai, Xiaohong Li, et al. "C-terminal domain of mammalian complexin-1 localizes to highly curved membranes." Proceedings of the National Academy of Sciences 113, no. 47 (2016): E7590—E7599. http://dx.doi.org/10.1073/pnas.1609917113.
Full textAbstract:
In presynaptic nerve terminals, complexin regulates spontaneous “mini” neurotransmitter release and activates Ca2+-triggered synchronized neurotransmitter release. We studied the role of the C-terminal domain of mammalian complexin in these processes using single-particle optical imaging and electrophysiology. The C-terminal domain is important for regulating spontaneous release in neuronal cultures and suppressing Ca2+-independent fusion in vitro, but it is not essential for evoked release in neuronal cultures and in vitro. This domain interacts with membranes in a curvature-dependent fashion similar to a previous study with worm complexin [Snead D, Wragg RT, Dittman JS, Eliezer D (2014) Membrane curvature sensing by the C-terminal domain of complexin. Nat Commun 5:4955]. The curvature-sensing value of the C-terminal domain is comparable to that of α-synuclein. Upon replacement of the C-terminal domain with membrane-localizing elements, preferential localization to the synaptic vesicle membrane, but not to the plasma membrane, results in suppression of spontaneous release in neurons. Membrane localization had no measurable effect on evoked postsynaptic currents of AMPA-type glutamate receptors, but mislocalization to the plasma membrane increases both the variability and the mean of the synchronous decay time constant of NMDA-type glutamate receptor evoked postsynaptic currents.
32
HENTSCHEL, H. G. E., and ALAN FINE. "COMPLEX BIOLOGICAL GROWTH: NEURONAL MORPHOGENESIS." Fractals 03, no. 04 (1995): 905–14. http://dx.doi.org/10.1142/s0218348x95000795.
Full textAbstract:
It has been observed that neurons and certain other cell types have dendritic arbors which appear to be self-similar. This biological pattern formation is consistent with the concept that shape is controlled by the local submembrane concentration of a morphogen believed to be the calcium ion. Such diffusion-controlled growth of the cellular cytoskeleton has recently been shown to lead to dendritic instabilities. Linear stability analysis suggests that dendritic arboring will be greatly enhanced in the presence of excitable membranes provided the cell is large enough. Computer simulations of this class of models have established many similarities to the growth and form of real neurons including a dendritic morphology reminicent of neuronal arbors and the existence of growth cones observed during real neuronal development; bioelectrical activity; effects of changes in membrane conductivity on morphology; galvanotropism; and chemotropism.
33
Marko, Daniel M., Gregory Foran, Filip Vlavcheski, et al. "Interleukin-6 Treatment Results in GLUT4 Translocation and AMPK Phosphorylation in Neuronal SH-SY5Y Cells." Cells 9, no. 5 (2020): 1114. http://dx.doi.org/10.3390/cells9051114.
Full textAbstract:
Interleukin-6 (IL-6) is a pleiotropic cytokine that can be released from the brain during prolonged exercise. In peripheral tissues, exercise induced IL-6 can result in GLUT4 translocation and increased glucose uptake through AMPK activation. GLUT4 is expressed in the brain and can be recruited to axonal plasma membranes with neuronal activity through AMPK activation. The aim of this study is to examine if IL-6 treatment: (1) results in AMPK activation in neuronal cells, (2) increases the activation of proteins involved in GLUT4 translocation, and (3) increases neuronal glucose uptake. Retinoic acid was used to differentiate SH-SY5Y neuronal cells. Treatment with 100 nM of insulin increased the phosphorylation of Akt and AS160 (p < 0.05). Treatment with 20 ng/mL of IL-6 resulted in the phosphorylation of STAT3 at Tyr705 (p ≤ 0.05) as well as AS160 (p < 0.05). Fluorescent Glut4GFP imaging revealed treatment with 20ng/mL of IL-6 resulted in a significant mobilization towards the plasma membrane after 5 min until 30 min. There was no difference in GLUT4 mobilization between the insulin and IL-6 treated groups. Importantly, IL-6 treatment increased glucose uptake. Our findings demonstrate that IL-6 and insulin can phosphorylate AS160 via different signaling pathways (AMPK and PI3K/Akt, respectively) and promote GLUT4 translocation towards the neuronal plasma membrane, resulting in increased neuronal glucose uptake in SH-SY5Y cells.
34
Momma, Yutaro, Mayumi Tsuji, Tatsunori Oguchi та ін. "The Curcumin Derivative GT863 Protects Cell Membranes in Cytotoxicity by Aβ Oligomers". International Journal of Molecular Sciences 24, № 4 (2023): 3089. http://dx.doi.org/10.3390/ijms24043089.
Full textAbstract:
In Alzheimer’s disease (AD), accumulation of amyloid β-protein (Aβ) is one of the major mechanisms causing neuronal cell damage. Disruption of cell membranes by Aβ has been hypothesized to be the important event associated with neurotoxicity in AD. Curcumin has been shown to reduce Aβ-induced toxicity; however, due to its low bioavailability, clinical trials showed no remarkable effect on cognitive function. As a result, GT863, a derivative of curcumin with higher bioavailability, was synthesized. The purpose of this study is to clarify the mechanism of the protective action of GT863 against the neurotoxicity of highly toxic Aβ oligomers (Aβo), which include high-molecular-weight (HMW) Aβo, mainly composed of protofibrils in human neuroblastoma SH-SY5Y cells, focusing on the cell membrane. The effect of GT863 (1 μM) on Aβo-induced membrane damage was assessed by phospholipid peroxidation of the membrane, membrane fluidity, membrane phase state, membrane potential, membrane resistance, and changes in intracellular Ca2+ ([Ca2+]i). GT863 inhibited the Aβo-induced increase in plasma-membrane phospholipid peroxidation, decreased membrane fluidity and resistance, and decreased excessive [Ca2+]i influx, showing cytoprotective effects. The effects of GT863 on cell membranes may contribute in part to its neuroprotective effects against Aβo-induced toxicity. GT863 may be developed as a prophylactic agent for AD by targeting inhibition of membrane disruption caused by Aβo exposure.
35
Jacob, M. H., J. M. Lindstrom, and D. K. Berg. "Surface and intracellular distribution of a putative neuronal nicotinic acetylcholine receptor." Journal of Cell Biology 103, no. 1 (1986): 205–14. http://dx.doi.org/10.1083/jcb.103.1.205.
Full textAbstract:
Chick ciliary ganglion neurons have a membrane component that shares an antigenic determinant with the main immunogenic region (MIR) of nicotinic acetylcholine receptors from skeletal muscle and electric organ. Previous studies have shown that the component has many of the properties expected for a ganglionic nicotinic acetylcholine receptor, and that its distribution on the neuron surface in vivo is restricted predominantly to synaptic membrane. Here we report the presence of a large intracellular pool of the putative receptor in embryonic neurons and demonstrate that it is associated with organelles known to comprise the biosynthetic and regulatory pathways of integral plasma membrane proteins. Embryonic chick ciliary ganglia were lightly fixed, saponin-permeabilized, incubated with an anti-MIR monoclonal antibody (mAb) followed by horseradish peroxidase-conjugated secondary antibody, reacted for peroxidase activity, and examined by electron microscopy. Deposits of reaction product were associated with synaptic membrane, small portions of the pseudodendrite surface membrane, most of the rough endoplasmic reticulum, small portions of the nuclear envelope, some Golgi complexes, and a few coated pits, coated vesicles, multivesicular bodies, and smooth-membraned vacuoles. No other labeling was present in the neurons. The labeling was specific in that it was not present when the anti-MIR mAb was replaced with either nonimmune serum or mAbs of different specificity. Chick dorsal root ganglion neurons thought to lack nicotinic acetylcholine receptors were not labeled by the anti-MIR mAb. Substantial intracellular populations have also been reported for the muscle acetylcholine receptor and brain voltage-dependent sodium channel alpha-subunit. This may represent a general pattern for multisubunit membrane proteins during development.
36
Oshikawa, Jin, Yoshiyuki Toya, Takayuki Fujita та ін. "Nicotinic acetylcholine receptor α7 regulates cAMP signal within lipid rafts". American Journal of Physiology-Cell Physiology 285, № 3 (2003): C567—C574. http://dx.doi.org/10.1152/ajpcell.00422.2002.
Full textAbstract:
Neuronal nicotinic acetylcholine receptors (nAChRs) are made of multiple subunits with diversified functions. The nAChR α7-subunit has a property of high Ca2+ permeability and may have specific functions and localization within the plasma membrane as a signal transduction molecule. In PC-12 cells, fractionation by sucrose gradient centrifugation revealed that nAChRα7 existed in low-density, cholesterol-enriched plasma membrane microdomains known as lipid rafts where flotillin also exists. In contrast, nAChR α5- and β2-subunits were located in high-density fractions, out of the lipid rafts. Type 6 adenylyl cyclase (AC6), a calcium-inhibitable isoform, was also found in lipid rafts and was coimmunoprecipitated with nAChRα7. Cholesterol depletion from plasma membranes with methyl-β-cyclodextrin redistributed nAChRα7 and AC6 diffusely within plasma membranes. Nicotine stimulation reduced forskolin-stimulated AC activity by 35%, and this inhibition was negated by either treatment with α-bungarotoxin, a specific antagonist of nAChRα7, or cholesterol depletion from plasma membranes. The effect of cholesterol depletion was negated by the addition of cholesterol. These data suggest that nAChRα7 has a specific membrane localization relative to other nAChR subunits and that lipid rafts are necessary to localize nAChRα7 with AC within plasma membranes. In addition, nAChRα7 may regulate the AC activity via Ca2+ within lipid rafts.
37
Chen, Xuanrui. "Neuronal membrane and Mechanisms Appeared on the Membrane Surface." BIO Web of Conferences 55 (2022): 01024. http://dx.doi.org/10.1051/bioconf/20225501024.
Full textAbstract:
Most mechanisms involved in neuronal maintenance and function are activated at the neuronal membrane. Membrane-related molecular agents, which interact in protein/lipid clusters to begin molecular processing and signal transduction, are required for these functions. Furthermore, many neuropathological disorders originate in this structure and/or are the result of membrane malfunction. Although the precise molecular mechanisms for maintaining "membrane health" are unknown in most cases, it appears that the effects of different lipids on the microstructural and stoichiometric properties of the membrane influence the behavior and association of proteins within the lipid environment, which determines the final cell response. This review is mainly focused on the function of neuronal membrane like substance exchange, cell signaling, etc.
38
Rudajev, Vladimir, та Jiri Novotny. "The Role of Lipid Environment in Ganglioside GM1-Induced Amyloid β Aggregation". Membranes 10, № 9 (2020): 226. http://dx.doi.org/10.3390/membranes10090226.
Full textAbstract:
Ganglioside GM1 is the most common brain ganglioside enriched in plasma membrane regions known as lipid rafts or membrane microdomains. GM1 participates in many modulatory and communication functions associated with the development, differentiation, and protection of neuronal tissue. It has, however, been demonstrated that GM1 plays a negative role in the pathophysiology of Alzheimer’s disease (AD). The two features of AD are the formation of intracellular neurofibrillary bodies and the accumulation of extracellular amyloid β (Aβ). Aβ is a peptide characterized by intrinsic conformational flexibility. Depending on its partners, Aβ can adopt different spatial arrangements. GM1 has been shown to induce specific changes in the spatial organization of Aβ, which lead to enhanced peptide accumulation and deleterious effect especially on neuronal membranes containing clusters of this ganglioside. Changes in GM1 levels and distribution during the development of AD may contribute to the aggravation of the disease.
39
Fomitcheva, Ioulia, and Danuta Kosk-Kosicka. "Volatile Anesthetics Selectively Inhibit the Calcium sup 2+ -transporting ATPase in Neuronal and Erythrocyte Plasma Membranes." Anesthesiology 84, no. 5 (1996): 1189–95. http://dx.doi.org/10.1097/00000542-199605000-00021.
Full textAbstract:
Background The activity of the plasma membrane Ca(2+)-transporting adenosine triphosphatase (PMCA) is inhibited by volatile anesthetics at clinical concentrations. The goal of the current study was to determine whether the inhibition is selective as compared to other adenosine triphosphatases (ATPases) and another group of general anesthetics, barbiturates. In addition, the authors determined whether the response to anesthetics of the enzymes in neuronal membranes is similar to that in erythrocyte membranes. Methods The effects of halothane, isoflurane, and sodium pentobarbital on four different ATPase activities were studied at 37 degrees C in two distinct plasma membrane preparations, human red blood cells and synaptosomal membranes from rat cerebellum. Results Inhibition patterns of the PMCA by halothane and isoflurane at anesthetic concentrations were vary similar in red blood cells and synaptosomal membranes. The half-maximal inhibition (I50) occurred at 0.25-0.30 mM halothane and 0.30-0.32 mM isoflurane. The PMCA in both membranes was significantly more sensitive to the inhibitory action of volatile anesthetics (I50 = 0.75-1.15 minimum alveolar concentration) than were other ATPases, such as the Na+,K+-ATPase (I50 approximately 3 minimum alveolar concentration) or Mg(2+)-ATPase (I50 &gt; or = 5 minimum alveolar concentration). In contrast, sodium pentobarbital inhibited the PMCA in both membranes only at approximately 100-200-fold above its anesthetic concentrations. The other ATPases were inhibited at similar pentobarbital concentrations (I50 = 11-22 mM). Conclusions The findings demonstrate analogous response of the PMCA of neuronal and erythrocyte cells to two groups of general anesthetics. The PMCA activity is selectively inhibited by volatile anesthetics at their clinical concentrations. The enzyme in vivo may then be a pharmacologic target for volatile anesthetics but not for barbiturates.
40
Bryant, Winnifred. "Modeling the Effects of Intracellular Anions on Membrane Potential: An Active-Learning Exercise." American Biology Teacher 81, no. 5 (2019): 373–76. http://dx.doi.org/10.1525/abt.2019.81.5.373.
Full textAbstract:
In biological membranes that are permeable to water and ions but impermeable to other solutes, the diffusible ions cannot reach a concentration equilibrium. Instead, a state of electroneutrality is achieved on each side of the membrane, which requires that the diffusible ions be found in different concentrations on either side of the membrane. The Donnan equilibrium is a major contributing factor to the polarized state of cells, and appreciating it is vital to the understanding of neuronal physiology. This article presents a nonmathematical active-learning exercise that will help AP and college biology students understand how the Donnan equilibrium is achieved.
41
ZOLI, MICHELE, DIEGO GUIDOLIN, KJELL FUXE, and LUIGI F. AGNATI. "THE RECEPTOR MOSAIC HYPOTHESIS OF THE ENGRAM: POSSIBLE RELEVANCE OF BOOLEAN NETWORK MODELING." International Journal of Neural Systems 07, no. 04 (1996): 363–68. http://dx.doi.org/10.1142/s0129065796000324.
Full textAbstract:
In the past 15 years, several lines of evidence have shown that receptors for chemical signals can interact in domains of the plasma membrane and possibly form molecular circuits encoding logical operators. In this frame, the receptor mosaic hypothesis of the engram was advanced. According to this proposal, aggregates of different receptor species (mosaics) may form in neuronal membranes (typically synapses) and constitute a memory trace (engram) of its activity. In the present paper, we present an attempt to model the functioning of aggregates of interacting receptors in membrane domains by means of random Boolean networks.
42
Csanaky, Katalin, Michael Hess, and Lars Klimaschewski. "Membrane-Associated, Not Cytoplasmic or Nuclear, FGFR1 Induces Neuronal Differentiation." Cells 8, no. 3 (2019): 243. http://dx.doi.org/10.3390/cells8030243.
Full textAbstract:
The intracellular transport of receptor tyrosine kinases results in the differential activation of various signaling pathways. In this study, optogenetic stimulation of fibroblast growth factor receptor type 1 (FGFR1) was performed to study the effects of subcellular targeting of receptor kinases on signaling and neurite outgrowth. The catalytic domain of FGFR1 fused to the algal light-oxygen-voltage-sensing (LOV) domain was directed to different cellular compartments (plasma membrane, cytoplasm and nucleus) in human embryonic kidney (HEK293) and pheochromocytoma (PC12) cells. Blue light stimulation elevated the pERK and pPLCγ1 levels in membrane-opto-FGFR1-transfected cells similarly to ligand-induced receptor activation; however, no changes in pAKT levels were observed. PC12 cells transfected with membrane-opto-FGFR1 exhibited significantly longer neurites after light stimulation than after growth factor treatment, and significantly more neurites extended from their cell bodies. The activation of cytoplasmic FGFR1 kinase enhanced ERK signaling in HEK293 cells but not in PC12 cells and did not induce neuronal differentiation. The stimulation of FGFR1 kinase in the nucleus also did not result in signaling changes or neurite outgrowth. We conclude that FGFR1 kinase needs to be associated with membranes to induce the differentiation of PC12 cells mainly via ERK activation.
43
Inthanon, Kewalin, Donraporn Daranarong, Pimwalan Techaikool, et al. "Biocompatibility Assessment of PLCL-Sericin Copolymer Membranes Using Wharton’s Jelly Mesenchymal Stem Cells." Stem Cells International 2016 (2016): 1–16. http://dx.doi.org/10.1155/2016/5309484.
Full textAbstract:
Stem cells based tissue engineering requires biocompatible materials, which allow the cells to adhere, expand, and differentiate in a large scale. An ideal biomaterial for clinical application should be free from mammalian products which cause immune reactivities and pathogen infections. We invented a novel biodegradable poly(L-lactic-co-ε-caprolactone)-sericin (PLCL-SC) copolymer membrane which was fabricated by electrospinning. Membranes with concentrations of 2.5 or 5% (w/v) SC exhibited qualified texture characteristics with a noncytotoxic release profile. The hydrophilic properties of the membranes were 35–40% higher than those of a standard PLCL and commercial polystyrene (PS). The improved characteristics of the membranes were due to an addition of new functional amide groups, C=O, N–H, and C–N, onto their surfaces. Degradation of the membranes was controllable, depending on the content proportion of SC. Results of thermogram indicated the superior stability and crystallinity of the membranes. These membranes enhanced human Wharton’s jelly mesenchymal stem cells (hWJMSC) proliferation by increasing cyclin A and also promoted cell adhesion by upregulating focal adhesion kinase (FAK). On the membranes, hWJMSC differentiated into a neuronal lineage with the occurrence ofnestin. These data suggest that PLCL-SC electrospun membrane represents some properties which will be useful for tissue engineering and medical applications.
44
Yang, Yoon-Sil, Moon-Suk Kang, Sun-Hee Kim, Su-Yong Eun, and Sung-Cherl Jung. "The changes of neuronal capacitance related resting membrane potential of CA1 hippocampal neurons of rats in developmental stages." Journal of Medicine and Life Science 8, no. 1 (2011): 42–45. http://dx.doi.org/10.22730/jmls.2011.8.1.42.
Full textAbstract:
In an early developmental stage within postnatal 3 weeks, neurons in mammalian brains shows dynamic and rapid changes of prolein expression on cellular membrane, related with ion channels and receptors. Using acute slices of rat hippocampi (postnatal 7-21), change of cell capacitance measured electrophysiologically during developmental stages have been studied to find the correlation with resting membrane potentials(RMP), which are decided by ion channel expression on neuronal membrane. The change of RMP showed significant changes to be hyperpolarized during developmental periods. However, the size of neurons was not significantly increased. This result indicates that, in an early developmental stage, developmental processings of neurons may be concentrated for modulating protein/lipid ratio of cellular membranes, rather than physical developments.
45
Ye, Hai-Bo, Hai-Bo Shi, and Shan-Kai Yin. "Mechanisms Underlying Taurine Protection Against Glutamate-Induced Neurotoxicity." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 40, no. 5 (2013): 628–34. http://dx.doi.org/10.1017/s0317167100014840.
Full textAbstract:
Abstract:Taurine appears to exert potent protections against glutamate (Glu)-induced injury to neurons, but the underlying molecular mechanisms are not fully understood. The possibly protected targets consist of the plasma membrane and the mitochondrial as well as endoplasmic reticulum (ER) membranes. Protection may be provided through a variety of effects, including the prevention of membrane depolarization, neuronal excitotoxicity and mitochondrial energy failure, increases in intracellular free calcium ([Ca2+]i), activation of calpain, and reduction of Bcl-2 levels. These activities are likely to be linked spatially and temporally in the neuroprotective functions of taurine. In addition, events that occur downstream of Glu stimulation, including altered enzymatic activities, apoptotic pathways, and necrosis triggered by the increased [Ca2+]i, can be inhibited by taurine. This review discusses the possible molecular mechanisms of taurine against Glu-induced neuronal injury, providing a better understanding of the protective processes, which might be helpful in the development of novel interventional strategies.
46
Feldstein, J. B., R. A. Gonzales, S. P. Baker, C. Sumners, F. T. Crews, and M. K. Raizada. "Decreased alpha 1-adrenergic receptor-mediated inositide hydrolysis in neurons from hypertensive rat brain." American Journal of Physiology-Cell Physiology 251, no. 2 (1986): C230—C237. http://dx.doi.org/10.1152/ajpcell.1986.251.2.c230.
Full textAbstract:
The expression of alpha 1-adrenergic receptors and norepinephrine (NE)-stimulated hydrolysis of inositol phospholipid has been studied in neuronal cultures from the brains of normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SH) rats. Binding of 125I-2-[beta-(4-hydroxyphenyl)-ethyl-aminomethyl] tetralone (HEAT) to neuronal membranes was 68-85% specific and was rapid. Competition-inhibition experiments with various agonists and antagonists suggested that 125I-HEAT bound selectively to alpha 1-adrenergic receptors. Specific binding of 125I-HEAT to neuronal membranes from SH rat brain cultures was 30-45% higher compared with binding in WKY normotensive controls. This increase was attributed to an increase in the number of alpha 1-adrenergic receptors on SH rat brain neurons. Incubation of neuronal cultures of rat brain from both strains with NE resulted in a concentration-dependent stimulation of release of inositol phosphates, although neurons from SH rat brains were 40% less responsive compared with WKY controls. The decrease in responsiveness of SH rat brain neurons to NE, even though the alpha 1-adrenergic receptors are increased, does not appear to be due to a general defect in membrane receptors and postreceptor signal transduction mechanisms. This is because neither the number of muscarinic-cholinergic receptors nor the carbachol-stimulated release of inositol phosphates is different in neuronal cultures from the brains of SH rats compared with neuronal cultures from the brains of WKY rats. These observations suggest that the increased expression of alpha 1-adrenergic receptors does not parallel the receptor-mediated inositol phosphate hydrolysis in neuronal cultures from SH rat brain.
47
Santos, Natalia, Luthary Segura, Amber Lewis, Thuong Pham, and Kwan H. Cheng. "Multiscale Modeling of Macromolecular Interactions between Tau-Amylin Oligomers and Asymmetric Lipid Nanodomains That Link Alzheimer’s and Diabetic Diseases." Molecules 29, no. 3 (2024): 740. http://dx.doi.org/10.3390/molecules29030740.
Full textAbstract:
The molecular events of protein misfolding and self-aggregation of tau and amylin are associated with the progression of Alzheimer’s and diabetes, respectively. Recent studies suggest that tau and amylin can form hetero-tau-amylin oligomers. Those hetero-oligomers are more neurotoxic than homo-tau oligomers. So far, the detailed interactions between the hetero-oligomers and the neuronal membrane are unknown. Using multiscale MD simulations, the lipid binding and protein folding behaviors of hetero-oligomers on asymmetric lipid nanodomains or raft membranes were examined. Our raft membranes contain phase-separated phosphatidylcholine (PC), cholesterol, and anionic phosphatidylserine (PS) or ganglioside (GM1) in one leaflet of the lipid bilayer. The hetero-oligomers bound more strongly to the PS and GM1 than other lipids via the hydrophobic and hydrophilic interactions, respectively, in the raft membranes. The hetero-tetramer disrupted the acyl chain orders of both PC and PS in the PS-containing raft membrane, but only the GM1 in the GM1-containing raft membrane as effectively as the homo-tau-tetramer. We discovered that the alpha-helical content in the heterodimer was greater than the sum of alpha-helical contents from isolated tau and amylin monomers on both raft membranes, indicative of a synergetic effect of tau-amylin interactions in surface-induced protein folding. Our results provide new molecular insights into understanding the cross-talk between Alzheimer’s and diabetes.
48
Herrera-Valdez, Marco Arieli. "An equation for the biological transmembrane potential from basic biophysical principles." F1000Research 9 (July 3, 2020): 676. http://dx.doi.org/10.12688/f1000research.24205.1.
Full textAbstract:
Biological membranes mediate different physiological processes necessary for life, many of which depend on ion movement. In turn, the difference between the electrical potentials around a biological membrane, called transmembrane potential, or membrane potential for short, is one of the key biophysical variables affecting ion movement. Most of the existing equations that describe the change in membrane potential are based on analogies with resistive-capacitive electrical circuits. These equivalent circuit models assume resistance and capacitance as measures of the permeable and the impermeable properties of the membrane, respectively. These models have increased our understanding of bioelectricity, and were particularly useful at times when the basic structure, biochemistry, and biophysics of biological membrane systems were not well known. However, the parts in the ohmic circuits from which equations are derived, are not quite like the biological elements present in the spaces around and within biological membranes. Using current, basic knowledge about the structure, biophysics, and biochemical properties of biological membrane systems, it is shown here that it is possible to derive a simple equation for the transmembrane potential. Of note, the resulting equation is not based on electrical circuit analogies. Nevertheless, the classical model for the membrane potential based on an equivalent RC-circuit is recovered as a particular case, thus providing a mathematical justification for the classical models. Examples are presented showing the effects of the voltage dependence of charge aggregation around the membrane, on the timing and shape of neuronal action potentials.
49
Lai, Ying, Ucheor B. Choi, Yunxiang Zhang, et al. "N-terminal domain of complexin independently activates calcium-triggered fusion." Proceedings of the National Academy of Sciences 113, no. 32 (2016): E4698—E4707. http://dx.doi.org/10.1073/pnas.1604348113.
Full textAbstract:
Complexin activates Ca2+-triggered neurotransmitter release and regulates spontaneous release in the presynaptic terminal by cooperating with the neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and the Ca2+-sensor synaptotagmin. The N-terminal domain of complexin is important for activation, but its molecular mechanism is still poorly understood. Here, we observed that a split pair of N-terminal and central domain fragments of complexin is sufficient to activate Ca2+-triggered release using a reconstituted single-vesicle fusion assay, suggesting that the N-terminal domain acts as an independent module within the synaptic fusion machinery. The N-terminal domain can also interact independently with membranes, which is enhanced by a cooperative interaction with the neuronal SNARE complex. We show by mutagenesis that membrane binding of the N-terminal domain is essential for activation of Ca2+-triggered fusion. Consistent with the membrane-binding property, the N-terminal domain can be substituted by the influenza virus hemagglutinin fusion peptide, and this chimera also activates Ca2+-triggered fusion. Membrane binding of the N-terminal domain of complexin therefore cooperates with the other fusogenic elements of the synaptic fusion machinery during Ca2+-triggered release.
50
Fusco, Giuliana, Serene W. Chen, Philip T. F. Williamson та ін. "Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers". Science 358, № 6369 (2017): 1440–43. http://dx.doi.org/10.1126/science.aan6160.
Full textAbstract:
Oligomeric species populated during the aggregation process of α-synuclein have been linked to neuronal impairment in Parkinson’s disease and related neurodegenerative disorders. By using solution and solid-state nuclear magnetic resonance techniques in conjunction with other structural methods, we identified the fundamental characteristics that enable toxic α-synuclein oligomers to perturb biological membranes and disrupt cellular function; these include a highly lipophilic element that promotes strong membrane interactions and a structured region that inserts into lipid bilayers and disrupts their integrity. In support of these conclusions, mutations that target the region that promotes strong membrane interactions by α-synuclein oligomers suppressed their toxicity in neuroblastoma cells and primary cortical neurons.