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Journal articles on the topic 'Progressive neurodegenerative diseases'
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1
de Paula, Caroline Zocatelli, Bruno Daniel Correia Gonçalves, and Luciene Bruno Vieira. "An Overview of Potential Targets for Treating Amyotrophic Lateral Sclerosis and Huntington’s Disease." BioMed Research International 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/198612.
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Neurodegenerative diseases affect millions of people worldwide. Progressive damage or loss of neurons, neurodegeneration, has severe consequences on the mental and physical health of a patient. Despite all efforts by scientific community, there is currently no cure or manner to slow degeneration progression. We review some treatments that attempt to prevent the progress of some of major neurodegenerative diseases: Amyotrophic Lateral Sclerosis and Huntington’s disease.
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Gao, Hui-Ming, and Jau-Shyong Hong. "Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression." Trends in Immunology 29, no. 8 (August 2008): 357–65. http://dx.doi.org/10.1016/j.it.2008.05.002.
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Alidoust, Leila, and Adele Jafari. "Exosomes: Future Perspective in Neurodegenerative Diseases." Caspian Journal of Neurological Sciences 6, no. 4 (October 1, 2020): 251–58. http://dx.doi.org/10.32598/cjns.6.23.4.
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Neurodegeneration is a progressive and irreversible loss of neuronal cells in specific regions of the brain. Alzheimer Diseases (AD) Parkinson Disease (PD) are the most common forms of neurodegenerative diseases in older people. Exosomes are extracellular nanovesicles that have a key role in physiological processes such as intercellular communication, cell migration, angiogenesis, and anti-tumor immunity. Mounting evidence indicates the role of exosomes in neurodegenerative disorders as possible carriers of disease particles. They have several different potential applications thanks to their unique structure and functions. The present review summarizes recent studies on exosome potentials as a biomarker and therapeutic tool in neurodegenerative diseases. It also provides an overview of the structure and function of exosomes.
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Ciaccio, Marcello. "Biochemical Biomarkers and Neurodegenerative Diseases." Brain Sciences 11, no. 7 (July 16, 2021): 940. http://dx.doi.org/10.3390/brainsci11070940.
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Neurodegenerative diseases (ND) are a heterogeneous group of disorders characterized by progressive dysfunction and loss of neurons in different areas of the central nervous system or peripheral nervous system [...]
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Nainu, Firzan, Emil Salim, Rangga Meidianto Asri, Aki Hori, and Takayuki Kuraishi. "Neurodegenerative disorders and sterile inflammation: lessons from a Drosophila model." Journal of Biochemistry 166, no. 3 (June 28, 2019): 213–21. http://dx.doi.org/10.1093/jb/mvz053.
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Abstract Central nervous system (CNS)-related disorders, including neurodegenerative diseases, are common but difficult to treat. As effective medical interventions are limited, those diseases will likely continue adversely affecting people’s health. There is evidence that the hyperactivation of innate immunity is a hallmark of most neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and polyglutamine diseases. In mammalian and fly CNS, the presence of noninfectious ligands, including danger-associated molecular patterns, is recognized by (micro)glial cells, inducing the expression of proinflammatory cytokines. Such inflammation may contribute to the onset and progression of neurodegenerative states. Studies using fruit flies have shed light on the types of signals, receptors and cells responsible for inducing the inflammation that leads to neurodegeneration. Researchers are using fly models to assess the mechanisms of sterile inflammation in the brain and its link to progressive neurodegeneration. Given the similarity of its physiological system and biochemical function to those of mammals, especially in activating and regulating innate immune signalling, Drosophila can be a versatile model system for studying the mechanisms and biological significance of sterile inflammatory responses in the pathogenesis of neurodegenerative diseases. Such knowledge would greatly facilitate the quest for a novel effective treatment for neurodegenerative diseases.
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Shrestha, R., Shakya Shrestha, O. Millington, J. Brewer, and T. Bushell. "Immune Responses in Neurodegenerative Diseases." Kathmandu University Medical Journal 12, no. 1 (October 12, 2015): 67–76. http://dx.doi.org/10.3126/kumj.v12i1.13646.
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Neurodegenerative disease is a progressive loss of neurons from central nervous system and has a huge impact on health care system. Various causes have been proposed of which inflammation has been suggested to be a probable key factor in the most of such conditions. The involvement of immune cells including lymphocytes in such diseased condition of the CNS supports this notion. The effective therapy for these diseases has been sought for more than a half century but still lacking such therapy. On such basis this review article has mainly focussed on evidence of the involvement of immune cells in various neurodegenerative diseases including Alzheimer’s disease, Parkinson’s diseases and Multiple sclerosis and suggests a possible therapy of such diseased conditions of the CNS by the modulation of immune system.Kathmandu University Medical Journal Vol.12(1) 2014: 67-76
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Li, Kelu, Zichao Chen, Yonggang Zhang, and Xinglong Yang. "Applications of iTRAQ and TMT Labeling Techniques to the Study of Neurodegenerative Diseases." Current Protein & Peptide Science 21, no. 12 (December 31, 2020): 1202–17. http://dx.doi.org/10.2174/1389203721666201103085704.
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: Neurodegenerative diseases are caused by progressive lesions or loss of specific nerve cells, which endanger human health. However, the mechanism by which neurodegeneration manifests remains unclear. Proteomics can shed light on this question as well as help establish diagnostic standards and discover new drug targets. The power of proteomics for understanding neurodegenerative diseases has increased substantially with the application of iTRAQ and TMT labeling techniques. This review focuses on progress in these labeling techniques and their applications in neurodegeneration research.
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Brkic, Marjana, Sriram Balusu, Claude Libert, and Roosmarijn E. Vandenbroucke. "Friends or Foes: Matrix Metalloproteinases and Their Multifaceted Roles in Neurodegenerative Diseases." Mediators of Inflammation 2015 (2015): 1–27. http://dx.doi.org/10.1155/2015/620581.
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Neurodegeneration is a chronic progressive loss of neuronal cells leading to deterioration of central nervous system (CNS) functionality. It has been shown that neuroinflammation precedes neurodegeneration in various neurodegenerative diseases. Matrix metalloproteinases (MMPs), a protein family of zinc-containing endopeptidases, are essential in (neuro)inflammation and might be involved in neurodegeneration. Although MMPs are indispensable for physiological development and functioning of the organism, they are often referred to as double-edged swords due to their ability to also inflict substantial damage in various pathological conditions. MMP activity is strictly controlled, and its dysregulation leads to a variety of pathologies. Investigation of their potential use as therapeutic targets requires a better understanding of their contributions to the development of neurodegenerative diseases. Here, we review MMPs and their roles in neurodegenerative diseases: Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), and multiple sclerosis (MS). We also discuss MMP inhibition as a possible therapeutic strategy to treat neurodegenerative diseases.
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Margiotta, Azzurra. "Role of SNAREs in Neurodegenerative Diseases." Cells 10, no. 5 (April 23, 2021): 991. http://dx.doi.org/10.3390/cells10050991.
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Neurodegenerative diseases are pathologies of the central and peripheral nervous systems characterized by loss of brain functions and problems in movement which occur due to the slow and progressive degeneration of cellular elements. Several neurodegenerative diseases are known such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis and many studies on the molecular mechanisms underlying these pathologies have been conducted. Altered functions of some key proteins and the presence of intraneuronal aggregates have been identified as responsible for the development of the diseases. Interestingly, the formation of the SNARE complex has been discovered to be fundamental for vesicle fusion, vesicle recycling and neurotransmitter release. Indeed, inhibition of the formation of the SNARE complex, defects in the SNARE-dependent exocytosis and altered regulation of SNARE-mediated vesicle fusion have been associated with neurodegeneration. In this review, the biological aspects of neurodegenerative diseases and the role of SNARE proteins in relation to the onset of these pathologies are described.
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Phadte, Ashutosh S., Zachary B. Sluzala, and Patrice E. Fort. "Therapeutic Potential of α-Crystallins in Retinal Neurodegenerative Diseases." Antioxidants 10, no. 7 (June 23, 2021): 1001. http://dx.doi.org/10.3390/antiox10071001.
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The chaperone and anti-apoptotic activity of α-crystallins (αA- and αB-) and their derivatives has received increasing attention due to their tremendous potential in preventing cell death. While originally known and described for their role in the lens, the upregulation of these proteins in cells and animal models of neurodegenerative diseases highlighted their involvement in adaptive protective responses to neurodegeneration associated stress. However, several studies also suggest that chronic neurodegenerative conditions are associated with progressive loss of function of these proteins. Thus, while external supplementation of α-crystallin shows promise, their potential as a protein-based therapeutic for the treatment of chronic neurodegenerative diseases remains ambiguous. The current review aims at assessing the current literature supporting the anti-apoptotic potential of αA- and αB-crystallins and its potential involvement in retinal neurodegenerative diseases. The review further extends into potentially modulating the chaperone and the anti-apoptotic function of α-crystallins and the use of such functionally enhanced proteins for promoting neuronal viability in retinal neurodegenerative disease.
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Licastro, Federico, and Elisa Porcellini. "Activation of Endogenous Retrovirus, Brain Infections and Environmental Insults in Neurodegeneration and Alzheimer’s Disease." International Journal of Molecular Sciences 22, no. 14 (July 6, 2021): 7263. http://dx.doi.org/10.3390/ijms22147263.
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Chronic neurodegenerative diseases are complex, and their pathogenesis is uncertain. Alzheimer’s disease (AD) is a neurodegenerative brain alteration that is responsible for most dementia cases in the elderly. AD etiology is still uncertain; however, chronic neuroinflammation is a constant component of brain pathology. Infections have been associated with several neurological diseases and viruses of the Herpes family appear to be a probable cause of AD neurodegenerative alterations. Several different factors may contribute to the AD clinical progression. Exogeneous viruses or other microbes and environmental pollutants may directly induce neurodegeneration by activating brain inflammation. In this paper, we suggest that exogeneous brain insults may also activate retrotransposons and silent human endogenous retroviruses (HERVs). The initial inflammation of small brain areas induced by virus infections or other brain insults may activate HERV dis-regulation that contributes to neurodegenerative mechanisms. Chronic HERV activation in turn may cause progressive neurodegeneration that thereafter merges in cognitive impairment and dementia in genetically susceptible people. Specific treatment for exogenous end endogenous pathogens and decreasing pollutant exposure may show beneficial effect in early intervention protocol to prevent the progression of cognitive deterioration in the elderly.
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Balana, Aaron T., and Matthew R. Pratt. "Mechanistic roles for altered O-GlcNAcylation in neurodegenerative disorders." Biochemical Journal 478, no. 14 (July 23, 2021): 2733–58. http://dx.doi.org/10.1042/bcj20200609.
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Neurodegenerative diseases such as Alzheimer's and Parkinson's remain highly prevalent and incurable disorders. A major challenge in fully understanding and combating the progression of these diseases is the complexity of the network of processes that lead to progressive neuronal dysfunction and death. An ideal therapeutic avenue is conceivably one that could address many if not all of these multiple misregulated mechanisms. Over the years, chemical intervention for the up-regulation of the endogenous posttranslational modification (PTM) O-GlcNAc has been proposed as a potential strategy to slow down the progression of neurodegeneration. Through the development and application of tools that allow dissection of the mechanistic roles of this PTM, there is now a growing body of evidence that O-GlcNAc influences a variety of important neurodegeneration-pertinent mechanisms, with an overall protective effect. As a PTM that is appended onto numerous proteins that participate in protein quality control and homeostasis, metabolism, bioenergetics, neuronal communication, inflammation, and programmed death, O-GlcNAc has demonstrated beneficence in animal models of neurodegenerative diseases, and its up-regulation is now being pursued in multiple clinical studies.
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Nayak, Annapurna, Rafia Ansar, Sunil K. Verma, Domenico Marco Bonifati, and Uday Kishore. "Huntington's Disease: An Immune Perspective." Neurology Research International 2011 (2011): 1–7. http://dx.doi.org/10.1155/2011/563784.
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Huntington's disease (HD) is a progressive neurodegenerative disorder that is caused by abnormal expansion of CAG trinucleotide repeats. Neuroinflammation is a typical feature of most neurodegenerative diseases that leads to an array of pathological changes within the affected areas in the brain. The neurodegeneration in HD is also caused by aberrant immune response in the presence of aggregated mutant huntingtin protein. The effects of immune activation in HD nervous system are a relatively unexplored area of research. This paper summarises immunological features associated with development and progression of HD.
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Hong, J. S. "O.107 Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression." Parkinsonism & Related Disorders 15 (December 2009): S28. http://dx.doi.org/10.1016/s1353-8020(09)70122-1.
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Mohd Sairazi, Nur Shafika, and K. N. S. Sirajudeen. "Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases." Evidence-Based Complementary and Alternative Medicine 2020 (February 14, 2020): 1–30. http://dx.doi.org/10.1155/2020/6565396.
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In recent years, natural products, which originate from plants, animals, and fungi, together with their bioactive compounds have been intensively explored and studied for their therapeutic potentials for various diseases such as cardiovascular, diabetes, hypertension, reproductive, cancer, and neurodegenerative diseases. Neurodegenerative diseases, including Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are characterized by the progressive dysfunction and loss of neuronal structure and function that resulted in the neuronal cell death. Since the multifactorial pathological mechanisms are associated with neurodegeneration, targeting multiple mechanisms of actions and neuroprotection approach, which involves preventing cell death and restoring the function to damaged neurons, could be promising strategies for the prevention and therapeutic of neurodegenerative diseases. Natural products have emerged as potential neuroprotective agents for the treatment of neurodegenerative diseases. This review focused on the therapeutic potential of natural products and their bioactive compounds to exert a neuroprotective effect on the pathologies of neurodegenerative diseases.
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Yaribeygi, Habib, Yunes Panahi, Behjat Javadi, and Amirhossein Sahebkar. "The Underlying Role of Oxidative Stress in Neurodegeneration: A Mechanistic Review." CNS & Neurological Disorders - Drug Targets 17, no. 3 (June 19, 2018): 207–15. http://dx.doi.org/10.2174/1871527317666180425122557.
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Background: Neurodegeneration is a condition in which progressive loss of function and structure of neurons occurs. Several lines of evidence suggest that oxidative stress has a central role in neurodegenerative diseases. Objective: The aim was to survey molecular mechanisms underlying the involvement of oxidative stress in developing different neurodegenerative diseases. Methods: Original and review articles were retrieved through a PubMed and Google scholar search (from 1989 to 2015) using the following key words: “oxidative stress”, “nerve degeneration” and “neurodegenerative diseases”. Results: A comprehensive analysis of the obtained articles confirmed strong involvement of oxidative stress in the pathophysiology of neurodegenerative diseases through a variety of mechanisms including induction of oxidation of nucleic acids, proteins and lipids, formation of advanced glycation end products, mitochondrial dysfunction, glial cell activation, amyloid β deposition and plaque formation, apoptosis, cytokine production and inflammatory responses, and proteasome dysfunction. Conclusion: Regarding the pivotal role of oxidative stress in neurodegeneration, modulation of free radical production or alleviating their harmful effects can be considered as a potential therapeutic strategy for preventing and controlling neurodegenerative diseases. Accordingly; boosting endogenous antioxidant capacity besides providing exogenous sources of antioxidants merits future research in order to discover new therapeutic agents.
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Maciejczyk, Mateusz, Anna Zalewska, and Karolina Gerreth. "Salivary Redox Biomarkers in Selected Neurodegenerative Diseases." Journal of Clinical Medicine 9, no. 2 (February 12, 2020): 497. http://dx.doi.org/10.3390/jcm9020497.
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Neurodegenerative diseases (NDDs), such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, are disorders, which cause irreversible and progressive deterioration of the central nervous system. The pathophysiology of NDDs is still not fully explained; nevertheless, oxidative stress is considered as a critical mediator of cerebral degeneration, brain inflammation, as well as neuronal apoptosis. Therefore, it is not surprising that redox biomarkers are increasingly used in the diagnosis of neurodegenerative diseases. As saliva is a very easy to obtain bioliquid, it seems promising to use this biomaterial in the diagnosis of NDDs. Saliva collection is easy, cheap, stress-free, and non-infectious, and it does not require the help of a specialised medical personnel. Additionally, the concentrations of many salivary redox biomarkers correlate with their content in blood serum as well as the degree of disease progression, which makes them non-invasive indicators of NDDs. This paper reviews the latest knowledge concerning the use of salivary redox biomarkers in the diagnosis and prognosis of selected neurodegenerative diseases.
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Coppedè, Fabio, Michelangelo Mancuso, Gabriele Siciliano, Lucia Migliore, and Luigi Murri. "Genes and the Environment in Neurodegeneration." Bioscience Reports 26, no. 5 (November 9, 2006): 341–67. http://dx.doi.org/10.1007/s10540-006-9028-6.
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Neurodegenerative diseases are a heterogeneous group of pathologies which includes complex multifactorial diseases, monogenic disorders and disorders for which inherited, sporadic and transmissible forms are known. Factors associated with predisposition and vulnerability to neurodegenerative disorders may be described usefully within the context of gene–environment interplay. There are many identified genetic determinants for neurodegeneration, and it is possible to duplicate many elements of recognized human neurodegenerative disorders in animal models of the disease. However, there are similarly several identifiable environmental influences on outcomes of the genetic defects; and the course of a progressive neurodegenerative disorder can be greatly modified by environmental elements. In this review we highlight some of the major neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's disease, and prion diseases.) and discuss possible links of gene–environment interplay including, where implicated, mitochondrial genes.
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Brown, Casey L., Alice Y. Hua, Lize De Coster, Virginia E. Sturm, Joel H. Kramer, Howard J. Rosen, Bruce L. Miller, and Robert W. Levenson. "Comparing two facets of emotion perception across multiple neurodegenerative diseases." Social Cognitive and Affective Neuroscience 15, no. 5 (May 2020): 511–22. http://dx.doi.org/10.1093/scan/nsaa060.
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Abstract Deficits in emotion perception (the ability to infer others’ emotions accurately) can occur as a result of neurodegeneration. It remains unclear how different neurodegenerative diseases affect different forms of emotion perception. The present study compares performance on a dynamic tracking task of emotion perception (where participants track the changing valence of a film character’s emotions) with performance on an emotion category labeling task (where participants label specific emotions portrayed by film characters) across seven diagnostic groups (N = 178) including Alzheimer’s disease (AD), behavioral variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA), non-fluent variant primary progressive aphasia (nfvPPA), progressive supranuclear palsy (PSP), corticobasal syndrome and healthy controls. Consistent with hypotheses, compared to controls, the bvFTD group was impaired on both tasks. The svPPA group was impaired on the emotion labeling task, whereas the nfvPPA, PSP and AD groups were impaired on the dynamic tracking task. Smaller volumes in bilateral frontal and left insular regions were associated with worse labeling, whereas smaller volumes in bilateral medial frontal, temporal and right insular regions were associated with worse tracking. Findings suggest labeling and tracking facets of emotion perception are differentially affected across neurodegenerative diseases due to their unique neuroanatomical correlates.
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Gupta, Rajaneesh, and Nilkantha Sen. "Traumatic brain injury: a risk factor for neurodegenerative diseases." Reviews in the Neurosciences 27, no. 1 (January 1, 2016): 93–100. http://dx.doi.org/10.1515/revneuro-2015-0017.
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AbstractTraumatic brain injury (TBI), a major global health and socioeconomic problem, is now established as a chronic disease process with a broad spectrum of pathophysiological symptoms followed by long-term disabilities. It triggers multiple and multidirectional biochemical events that lead to neurodegeneration and cognitive impairment. Recent studies have presented strong evidence that patients with TBI history have a tendency to develop proteinopathy, which is the pathophysiological feature of neurodegenerative disorders such as Alzheimer disease (AD), chronic traumatic encephalopathy (CTE), and amyotrophic lateral sclerosis (ALS). This review mainly focuses on mechanisms related to AD, CTE, and ALS that are induced after TBI and their relevance to the advancement of these neurodegenerative diseases. This review encompasses acute effects and chronic neurodegenerative consequences after TBI for a better understanding of TBI-induced neuronal death and to design therapies that will effectively treat patients in the primary or secondary progressive stages.
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Torrente, Yvan, and Elio Polli. "Mesenchymal Stem Cell Transplantation for Neurodegenerative Diseases." Cell Transplantation 17, no. 10-11 (October 2008): 1103–13. http://dx.doi.org/10.3727/096368908787236576.
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Neurodegenerative diseases are characterized by a progressive degeneration of selective neural populations. The lack of effective treatment and the characteristic of their pathology make these diseases appropriate candidates for cell therapy. Mesenchymal stem cells (MSCs) are multipotent stem-like cells that are capable of differentiating into mesenchymal and nonmesenchymal lineages. Their regenerative capacity after in vivo transplantation into animal models of neurodegenerative diseases has suggested that they could be useful against human diseases. Human bone marrow-derived MSCs (hMSCs) can be easily amplified in vitro and their transdifferentiation has been claimed in vitro and in vivo in neural cells. There are some doubts concerning the exact mechanisms responsible for the beneficial outcome observed after MSC transplantation into neurodegenerating tissues. Possible interpretations include cell replacement, trophic factor delivery, and immunomodulation. This review mainly concerns hMSCs transplantation in neurodegenerative diseases, because it has proven to be feasible, safe, and potentially effective. Although they have been used in hundreds of clinical trials, mixed results and no functional and long-lasting integration have so far been observed. hMSCs transplantations therefore still have their “dark side.” However, the challenge in well-planned clinical trials merits discussion.
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Rozpędek-Kamińska, Wioletta, Natalia Siwecka, Adam Wawrzynkiewicz, Radosław Wojtczak, Dariusz Pytel, J. Alan Diehl, and Ireneusz Majsterek. "The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases." International Journal of Molecular Sciences 21, no. 6 (March 19, 2020): 2108. http://dx.doi.org/10.3390/ijms21062108.
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Higher prevalence of neurodegenerative diseases is strictly connected with progressive aging of the world population. Interestingly, a broad range of age-related, neurodegenerative diseases is characterized by a common pathological mechanism—accumulation of misfolded and unfolded proteins within the cells. Under certain circumstances, such protein aggregates may evoke endoplasmic reticulum (ER) stress conditions and subsequent activation of the unfolded protein response (UPR) signaling pathways via the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-dependent manner. Under mild to moderate ER stress, UPR has a pro-adaptive role. However, severe or long-termed ER stress conditions directly evoke shift of the UPR toward its pro-apoptotic branch, which is considered to be a possible cause of neurodegeneration. To this day, there is no effective cure for Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), or prion disease. Currently available treatment approaches for these diseases are only symptomatic and cannot affect the disease progression. Treatment strategies, currently under detailed research, include inhibition of the PERK-dependent UPR signaling branches. The newest data have reported that the use of small-molecule inhibitors of the PERK-mediated signaling branches may contribute to the development of a novel, ground-breaking therapeutic approach for neurodegeneration. In this review, we critically describe all the aspects associated with such targeted therapy against neurodegenerative proteopathies.
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Catanesi, Mariano, Michele d’Angelo, Maria Grazia Tupone, Elisabetta Benedetti, Antonio Giordano, Vanessa Castelli, and Annamaria Cimini. "MicroRNAs Dysregulation and Mitochondrial Dysfunction in Neurodegenerative Diseases." International Journal of Molecular Sciences 21, no. 17 (August 20, 2020): 5986. http://dx.doi.org/10.3390/ijms21175986.
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Neurodegenerative diseases are debilitating and currently incurable conditions causing severe cognitive and motor impairments, defined by the progressive deterioration of neuronal structure and function, eventually causing neuronal loss. Understand the molecular and cellular mechanisms underlying these disorders are essential to develop therapeutic approaches. MicroRNAs (miRNAs) are short non-coding RNAs implicated in gene expression regulation at the post-transcriptional level. Moreover, miRNAs are crucial for different processes, including cell growth, signal transmission, apoptosis, cancer and aging-related neurodegenerative diseases. Altered miRNAs levels have been associated with the formation of reactive oxygen species (ROS) and mitochondrial dysfunction. Mitochondrial dysfunction and ROS formation occur in many neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases. The crosstalk existing among oxidative stress, mitochondrial dysfunction and miRNAs dysregulation plays a pivotal role in the onset and progression of neurodegenerative diseases. Based on this evidence, in this review, with a focus on miRNAs and their role in mitochondrial dysfunction in aging-related neurodegenerative diseases, with a focus on their potential as diagnostic biomarkers and therapeutic targets.
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Mirahmadi, Mahdi, Habib Rezanejadbardaji, Muhammad Irfan-Maqsood, Mohammad Javad Mokhtari, and Hojjat Naderi-Meshkin. "Stem Cell Therapy for Neurodegenerative Diseases: Strategies for Regeneration against Degeneration." Journal of Genes and Cells 3 (April 15, 2017): 22. http://dx.doi.org/10.15562/gnc.54.
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Neurodegeneration is a general term for the progressive loss of structure and/ or function of neurons, gives rise to dysfunction or death of neurons. Neurodegenerative diseases including Alzheimer´s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), spinal cord injury (SCI) and brain ischemia (BI) occur as a result of neurodegenerative processes leading to different degrees of paralysis and loss of sensation and cognition in the patients. Unfortunately, no successful cure for neurodegenerative disorders has been developed so far, and most of the currently available pharmacological therapies are mainly palliative. In recent years, stem cells have provided a great opportunity to develop potentially powerful innovative strategies to cure neurodegenerative diseases. Stem cells transplantation is capable of restoring injured neuronal tissue by replacement of the damaged cells via using directly differentiated cells or by protecting of existing healthy neurons and glial cells from further damage, or by repairing through providing a conductive environment in favour of regeneration. Here we have brought together some of these examples, discuss possible therapeutic means using different types of stem cells, mainly adult stem cells (ASCs), to treat neurodegenerative diseases.
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Silvestro, Serena, Cinzia Sindona, Placido Bramanti, and Emanuela Mazzon. "A State of the Art of Antioxidant Properties of Curcuminoids in Neurodegenerative Diseases." International Journal of Molecular Sciences 22, no. 6 (March 20, 2021): 3168. http://dx.doi.org/10.3390/ijms22063168.
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Neurodegenerative diseases represent a set of pathologies characterized by an irreversible and progressive, and a loss of neuronal cells in specific areas of the brain. Oxidative phosphorylation is a source of energy production by which many cells, such as the neuronal cells, meet their energy needs. Dysregulations of oxidative phosphorylation induce oxidative stress, which plays a key role in the onset of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). To date, for most neurodegenerative diseases, there are no resolute treatments, but only interventions capable of alleviating the symptoms or slowing the course of the disease. Therefore, effective neuroprotection strategies are needed. In recent years, natural products, such as curcuminoids, have been intensively explored and studied for their therapeutic potentials in several neurodegenerative diseases. Curcuminoids are, nutraceutical compouns, that owen several therapeutic properties such as anti-oxidant, anti-inflammatory and neuroprotective effects. In this context, the aim of this review was to provide an overview of preclinical and clinical evidence aimed to illustrate the antioxidant effects of curcuminoids in neurodegenerative diseases. Promising results from preclinical studies encourage the use of curcuminoids for neurodegeneration prevention and treatment.
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Van Bulck, Michiel, Ana Sierra-Magro, Jesus Alarcon-Gil, Ana Perez-Castillo, and Jose Morales-Garcia. "Novel Approaches for the Treatment of Alzheimer’s and Parkinson’s Disease." International Journal of Molecular Sciences 20, no. 3 (February 8, 2019): 719. http://dx.doi.org/10.3390/ijms20030719.
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Neurodegenerative disorders affect around one billion people worldwide. They can arise from a combination of genomic, epigenomic, metabolic, and environmental factors. Aging is the leading risk factor for most chronic illnesses of old age, including Alzheimer’s and Parkinson’s diseases. A progressive neurodegenerative process and neuroinflammation occur, and no current therapies can prevent, slow, or halt disease progression. To date, no novel disease-modifying therapies have been shown to provide significant benefit for patients who suffer from these devastating disorders. Therefore, early diagnosis and the discovery of new targets and novel therapies are of upmost importance. Neurodegenerative diseases, like in other age-related disorders, the progression of pathology begins many years before the onset of symptoms. Many efforts in this field have led to the conclusion that exits some similar events among these diseases that can explain why the aging brain is so vulnerable to suffer neurodegenerative diseases. This article reviews the current knowledge about these diseases by summarizing the most common features of major neurodegenerative disorders, their causes and consequences, and the proposed novel therapeutic approaches.
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Fan, Dahua, Liping Liu, Zhengzhi Wu, and Meiqun Cao. "Combating Neurodegenerative Diseases with the Plant Alkaloid Berberine: Molecular Mechanisms and Therapeutic Potential." Current Neuropharmacology 17, no. 6 (May 9, 2019): 563–79. http://dx.doi.org/10.2174/1570159x16666180419141613.
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Neurodegenerative diseases are among the most serious health problems affecting millions of people worldwide. Such diseases are characterized by a progressive degeneration and / or death of neurons in the central nervous system. Currently, there are no therapeutic approaches to cure or even halt the progression of neurodegenerative diseases. During the last two decades, much attention has been paid to the neuroprotective and anti-neurodegenerative activities of compounds isolated from natural products with high efficacy and low toxicity. Accumulating evidence indicates that berberine, an isoquinoline alkaloid isolated from traditional Chinese medicinal herbs, may act as a promising anti-neurodegenerative agent by inhibiting the activity of the most important pathogenic enzymes, ameliorating intracellular oxidative stress, attenuating neuroinflammation, triggering autophagy and protecting neurons against apoptotic cell death. This review attempts to summarize the current state of knowledge regarding the therapeutic potential of berberine against neurodegenerative diseases, with a focus on the molecular mechanisms that underlie its effects on Alzheimer’s, Parkinson’s and Huntington’s diseases.
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Zhunina, Olga A., Nikita G. Yabbarov, Andrey V. Grechko, Shaw-Fang Yet, Igor A. Sobenin, and Alexander N. Orekhov. "Neurodegenerative Diseases Associated with Mitochondrial DNA Mutations." Current Pharmaceutical Design 26, no. 1 (February 25, 2020): 103–9. http://dx.doi.org/10.2174/1381612825666191122091320.
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Mitochondrial dysfunction underlies several human chronic pathologies, including cardiovascular disorders, cancers and neurodegenerative diseases. Impaired mitochondrial function associated with oxidative stress can be a result of both nuclear and mitochondrial DNA (mtDNA) mutations. Neurological disorders associated with mtDNA mutations include mitochondrial encephalomyopathy, chronic progressive external ophthalmoplegia, neurogenic weakness, and Leigh syndrome. Moreover, mtDNA mutations were shown to play a role in the development of Parkinson and Alzheimer’s diseases. In this review, current knowledge on the distribution and possible roles of mtDNA mutations in the onset and development of various neurodegenerative diseases, with special focus on Parkinson’s and Alzheimer’s diseases has been discussed.
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Gupta, Swapnil, Panpan You, Tanima SenGupta, Hilde Nilsen, and Kulbhushan Sharma. "Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases." Biology 10, no. 2 (February 19, 2021): 163. http://dx.doi.org/10.3390/biology10020163.
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Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.
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Costantini, Erica, Chiara D’Angelo, and Marcella Reale. "The Role of Immunosenescence in Neurodegenerative Diseases." Mediators of Inflammation 2018 (2018): 1–12. http://dx.doi.org/10.1155/2018/6039171.
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Aging is characterized by the progressive decline of physiological function and tissue homeostasis leading to increased vulnerability, degeneration, and death. Aging-related changes of the innate and adaptive immune system include decline in the preservation and enhancement of many immune functions, such as changes in the number of circulating monocytic and dendritic cells, thymic involution, T cell polyfunctionality, or production of proinflammatory cytokines, and are defined as immunosenescence. Inflammatory functions are increased with age, causing the chronic low-grade inflammation, referred to as inflamm-aging, that contribute, together with immunosenescence, to neurodegenerative diseases. In this review, we discuss the link between the immune and nervous systems and how the immunosenescence and inflamm-aging can contribute to neurodegenerative diseases.
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Halloran, M., S. Parakh, and J. D. Atkin. "The Role of S-Nitrosylation and S-Glutathionylation of Protein Disulphide Isomerase in Protein Misfolding and Neurodegeneration." International Journal of Cell Biology 2013 (2013): 1–15. http://dx.doi.org/10.1155/2013/797914.
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Neurodegenerative diseases involve the progressive loss of neurons, and a pathological hallmark is the presence of abnormal inclusions containing misfolded proteins. Although the precise molecular mechanisms triggering neurodegeneration remain unclear, endoplasmic reticulum (ER) stress, elevated oxidative and nitrosative stress, and protein misfolding are important features in pathogenesis. Protein disulphide isomerase (PDI) is the prototype of a family of molecular chaperones and foldases upregulated during ER stress that are increasingly implicated in neurodegenerative diseases. PDI catalyzes the rearrangement and formation of disulphide bonds, thus facilitating protein folding, and in neurodegeneration may act to ameliorate the burden of protein misfolding. However, an aberrant posttranslational modification of PDI, S-nitrosylation, inhibits its protective function in these conditions. S-nitrosylation is a redox-mediated modification that regulates protein function by covalent addition of nitric oxide- (NO-) containing groups to cysteine residues. Here, we discuss the evidence for abnormal S-nitrosylation of PDI (SNO-PDI) in neurodegeneration and how this may be linked to another aberrant modification of PDI, S-glutathionylation. Understanding the role of aberrant S-nitrosylation/S-glutathionylation of PDI in the pathogenesis of neurodegenerative diseases may provide insights into novel therapeutic interventions in the future.
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Su, Yun, Liyuan Fan, Changhe Shi, Tai Wang, Huimin Zheng, Haiyang Luo, Shuo Zhang, et al. "Deciphering Neurodegenerative Diseases Using Long-Read Sequencing." Neurology 97, no. 9 (August 13, 2021): 423–33. http://dx.doi.org/10.1212/wnl.0000000000012466.
Full textAbstract:
Neurodegenerative diseases exhibit chronic progressive lesions in the central and peripheral nervous systems with unclear causes. The search for pathogenic mutations in human neurodegenerative diseases has benefited from massively parallel short-read sequencers. However, genomic regions, including repetitive elements, especially with high/low GC content, are far beyond the capability of conventional approaches. Recently, long-read single-molecule DNA sequencing technologies have emerged and enabled researchers to study genomes, transcriptomes, and metagenomes at unprecedented resolutions. The identification of novel mutations in unresolved neurodegenerative disorders, the characterization of causative repeat expansions, and the direct detection of epigenetic modifications on naive DNA by virtue of long-read sequencers will further expand our understanding of neurodegenerative diseases. In this article, we review and compare 2 prevailing long-read sequencing technologies, Pacific Biosciences and Oxford Nanopore Technologies, and discuss their applications in neurodegenerative diseases.
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Koziorowski, Dariusz, Monika Figura, Łukasz M. Milanowski, Stanisław Szlufik, Piotr Alster, Natalia Madetko, and Andrzej Friedman. "Mechanisms of Neurodegeneration in Various Forms of Parkinsonism—Similarities and Differences." Cells 10, no. 3 (March 16, 2021): 656. http://dx.doi.org/10.3390/cells10030656.
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Parkinson’s disease (PD), dementia with Lewy body (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) belong to a group of neurodegenerative diseases called parkinsonian syndromes. They share several clinical, neuropathological and genetic features. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra- and intracellular accumulation of misfolded proteins. The parkinsonian diseases affect distinct areas of the brain. PD and MSA belong to a group of synucleinopathies that are characterized by the presence of fibrillary aggregates of α-synuclein protein in the cytoplasm of selected populations of neurons and glial cells. PSP is a tauopathy associated with the pathological aggregation of the microtubule associated tau protein. Although PD is common in the world’s aging population and has been extensively studied, the exact mechanisms of the neurodegeneration are still not fully understood. Growing evidence indicates that parkinsonian disorders to some extent share a genetic background, with two key components identified so far: the microtubule associated tau protein gene (MAPT) and the α-synuclein gene (SNCA). The main pathways of parkinsonian neurodegeneration described in the literature are the protein and mitochondrial pathways. The factors that lead to neurodegeneration are primarily environmental toxins, inflammatory factors, oxidative stress and traumatic brain injury.
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Barcelos, Isabella Peixoto de, Regina M. Troxell, and Jennifer S. Graves. "Mitochondrial Dysfunction and Multiple Sclerosis." Biology 8, no. 2 (May 11, 2019): 37. http://dx.doi.org/10.3390/biology8020037.
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In recent years, several studies have examined the potential associations between mitochondrial dysfunction and neurodegenerative diseases such as multiple sclerosis (MS), Parkinson’s disease and Alzheimer’s disease. In MS, neurological disability results from inflammation, demyelination, and ultimately, axonal damage within the central nervous system. The sustained inflammatory phase of the disease leads to ion channel changes and chronic oxidative stress. Several independent investigations have demonstrated mitochondrial respiratory chain deficiency in MS, as well as abnormalities in mitochondrial transport. These processes create an energy imbalance and contribute to a parallel process of progressive neurodegeneration and irreversible disability. The potential roles of mitochondria in neurodegeneration are reviewed. An overview of mitochondrial diseases that may overlap with MS are also discussed, as well as possible therapeutic targets for the treatment of MS and other neurodegenerative conditions.
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Qin, Siru, Huiling Tang, Wei Li, Yinan Gong, Shanshan Li, Jin Huang, Yuxin Fang, et al. "AMPK and its Activator Berberine in the Treatment of Neurodegenerative Diseases." Current Pharmaceutical Design 26, no. 39 (November 10, 2020): 5054–66. http://dx.doi.org/10.2174/1381612826666200523172334.
Full textAbstract:
Neurodegenerative disorders are heterogeneous diseases associated with either acute or progressive neurodegeneration, causing the loss of neurons and axons in the central nervous system (CNS), showing high morbidity and mortality, and there are only a few effective therapies. Here, we summarized that the energy sensor adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK), and its agonist berberine can combat the common underlying pathological events of neurodegeneration, including oxidative stress, neuroinflammation, mitochondrial disorder, glutamate excitotoxicity, apoptosis, autophagy disorder, and disruption of neurovascular units. The abovementioned effects of berberine may primarily depend on activating AMPK and its downstream targets, such as the mammalian target of rapamycin (mTOR), sirtuin1 (SIRT1), nuclear factor erythroid-2 related factor-2 (Nrf2), nuclear factor-κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), nicotinamide adenine dinucleotide (NAD+), and p38 mitogen-activated protein kinase (p38 MAPK). It is hoped that this review will provide a strong basis for further scientific exploration and development of berberine #039;s therapeutic potential against neurodegeneration.
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Gámez-Valero, Ana, Anna Guisado-Corcoll, Marina Herrero-Lorenzo, Maria Solaguren-Beascoa, and Eulàlia Martí. "Non-Coding RNAs as Sensors of Oxidative Stress in Neurodegenerative Diseases." Antioxidants 9, no. 11 (November 8, 2020): 1095. http://dx.doi.org/10.3390/antiox9111095.
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Oxidative stress (OS) results from an imbalance between the production of reactive oxygen species and the cellular antioxidant capacity. OS plays a central role in neurodegenerative diseases, where the progressive accumulation of reactive oxygen species induces mitochondrial dysfunction, protein aggregation and inflammation. Regulatory non-protein-coding RNAs (ncRNAs) are essential transcriptional and post-transcriptional gene expression controllers, showing a highly regulated expression in space (cell types), time (developmental and ageing processes) and response to specific stimuli. These dynamic changes shape signaling pathways that are critical for the developmental processes of the nervous system and brain cell homeostasis. Diverse classes of ncRNAs have been involved in the cell response to OS and have been targeted in therapeutic designs. The perturbed expression of ncRNAs has been shown in human neurodegenerative diseases, with these changes contributing to pathogenic mechanisms, including OS and associated toxicity. In the present review, we summarize existing literature linking OS, neurodegeneration and ncRNA function. We provide evidences for the central role of OS in age-related neurodegenerative conditions, recapitulating the main types of regulatory ncRNAs with roles in the normal function of the nervous system and summarizing up-to-date information on ncRNA deregulation with a direct impact on OS associated with major neurodegenerative conditions.
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Polajnar, Mira, and Eva Žerovnik. "Impaired autophagy: a link between neurodegenerative diseases and progressive myoclonus epilepsies." Trends in Molecular Medicine 17, no. 6 (June 2011): 293–300. http://dx.doi.org/10.1016/j.molmed.2011.02.005.
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Kabir, Md Tanvir, Md Sahab Uddin, Ahmed Abdeen, Ghulam Md Ashraf, Asma Perveen, Abdul Hafeez, May N. Bin-Jumah, and Mohamed M. Abdel-Daim. "Evidence Linking Protein Misfolding to Quality Control in Progressive Neurodegenerative Diseases." Current Topics in Medicinal Chemistry 20, no. 23 (October 12, 2020): 2025–43. http://dx.doi.org/10.2174/1568026620666200618114924.
Full textAbstract:
Several proteolytic systems including ubiquitin (Ub)-proteasome system (UPS), chaperonemediated autophagy (CMA), and macroautophagy are used by the mammalian cells to remove misfolded proteins (MPs). UPS mediates degradation of most of the MPs, where Ub-conjugated substrates are deubiquitinated, unfolded, and passed through the proteasome’s narrow chamber, and eventually break into smaller peptides. It has been observed that the substrates that show a specific degradation signal, the KFERQ sequence motif, can be delivered to and go through CMA-mediated degradation in lysosomes. Macroautophagy can help in the degradation of substrates that are prone to aggregation and resistant to both the CMA and UPS. In the aforesaid case, cargoes are separated into autophagosomes before lysosomal hydrolase-mediated degradation. Even though the majority of the aggregated and MPs in the human proteome can be removed via cellular protein quality control (PQC), some mutant and native proteins tend to aggregate into β-sheet-rich oligomers that exhibit resistance to all identified proteolytic processes and can, therefore, grow into extracellular plaques or inclusion bodies. Indeed, the buildup of protease-resistant aggregated and MPs is a usual process underlying various protein misfolding disorders, including neurodegenerative diseases (NDs) for example Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and prion diseases. In this article, we have focused on the contribution of PQC in the degradation of pathogenic proteins in NDs.
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Paraskevaidi, Maria, Camilo L. M. Morais, Kássio M. G. Lima, Julie S. Snowden, Jennifer A. Saxon, Anna M. T. Richardson, Matthew Jones, et al. "Differential diagnosis of Alzheimer’s disease using spectrochemical analysis of blood." Proceedings of the National Academy of Sciences 114, no. 38 (September 5, 2017): E7929—E7938. http://dx.doi.org/10.1073/pnas.1701517114.
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The progressive aging of the world’s population makes a higher prevalence of neurodegenerative diseases inevitable. The necessity for an accurate, but at the same time, inexpensive and minimally invasive, diagnostic test is urgently required, not only to confirm the presence of the disease but also to discriminate between different types of dementia to provide the appropriate management and treatment. In this study, attenuated total reflection FTIR (ATR-FTIR) spectroscopy combined with chemometric techniques were used to analyze blood plasma samples from our cohort. Blood samples are easily collected by conventional venepuncture, permitting repeated measurements from the same individuals to monitor their progression throughout the years or evaluate any tested drugs. We included 549 individuals: 347 with various neurodegenerative diseases and 202 age-matched healthy individuals. Alzheimer’s disease (AD;n= 164) was identified with 70% sensitivity and specificity, which after the incorporation of apolipoprotein ε4 genotype (APOEε4) information, increased to 86% when individuals carried one or two alleles of ε4, and to 72% sensitivity and 77% specificity when individuals did not carry ε4 alleles. Early AD cases (n= 14) were identified with 80% sensitivity and 74% specificity. Segregation of AD from dementia with Lewy bodies (DLB;n= 34) was achieved with 90% sensitivity and specificity. Other neurodegenerative diseases, such as frontotemporal dementia (FTD;n= 30), Parkinson’s disease (PD;n= 32), and progressive supranuclear palsy (PSP;n= 31), were included in our cohort for diagnostic purposes. Our method allows for both rapid and robust diagnosis of neurodegeneration and segregation between different dementias.
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Zugaza, José L. "Cell Signaling in Neurodegeneration." International Journal of Molecular Sciences 22, no. 16 (August 20, 2021): 8978. http://dx.doi.org/10.3390/ijms22168978.
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Michalska, Patrycja, and Rafael León. "When It Comes to an End: Oxidative Stress Crosstalk with Protein Aggregation and Neuroinflammation Induce Neurodegeneration." Antioxidants 9, no. 8 (August 12, 2020): 740. http://dx.doi.org/10.3390/antiox9080740.
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Neurodegenerative diseases are characterized by a progressive loss of neurons in the brain or spinal cord that leads to a loss of function of the affected areas. The lack of effective treatments and the ever-increasing life expectancy is raising the number of individuals affected, having a tremendous social and economic impact. The brain is particularly vulnerable to oxidative damage given the high energy demand, low levels of antioxidant defenses, and high levels of metal ions. Driven by age-related changes, neurodegeneration is characterized by increased oxidative stress leading to irreversible neuronal damage, followed by cell death. Nevertheless, neurodegenerative diseases are known as complex pathologies where several mechanisms drive neuronal death. Herein we discuss the interplay among oxidative stress, proteinopathy, and neuroinflammation at the early stages of neurodegenerative diseases. Finally, we discuss the use of the Nrf2-ARE pathway as a potential therapeutic strategy based on these molecular mechanisms to develop transformative medicines.
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Hannan, Anthony J. "Molecular mediators, environmental modulators and experience-dependent synaptic dysfunction in Huntington's disease." Acta Biochimica Polonica 51, no. 2 (June 30, 2004): 415–30. http://dx.doi.org/10.18388/abp.2004_3581.
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Huntington's disease (HD) is an autosomal dominant disorder in which there is progressive neurodegeneration producing motor, cognitive and psychiatric symptoms. HD is caused by a trinucleotide (CAG) repeat mutation, encoding an expanded polyglutamine tract in the huntingtin protein. At least eight other neurodegenerative diseases are caused by CAG/glutamine repeat expansions in different genes. Recent evidence suggests that environmental factors can modify the onset and progression of Huntington's disease and possibly other neurodegenerative disorders. This review outlines possible molecular and cellular mechanisms mediating the polyglutamine-induced toxic 'gain of function' and associated gene-environment interactions in HD. Key aspects of pathogenesis shared with other neurodegenerative diseases may include abnormal protein-protein interactions, selective disruption of gene expression and 'pathological plasticity' of synapses in specific brain regions. Recent discoveries regarding molecular mechanisms of pathogenesis are guiding the development of new therapeutic approaches. Knowledge of gene-environment interactions, for example, could lead to development of 'enviromimetics' which mimic the beneficial effects of specific environmental stimuli. The effects of environmental enrichment on brain and behaviour will also be discussed, together with the general implications for neuroscience research involving animal models.
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Tonoki, Ayako, Erina Kuranaga, Takeyasu Tomioka, Jun Hamazaki, Shigeo Murata, Keiji Tanaka, and Masayuki Miura. "Genetic Evidence Linking Age-Dependent Attenuation of the 26S Proteasome with the Aging Process." Molecular and Cellular Biology 29, no. 4 (December 15, 2008): 1095–106. http://dx.doi.org/10.1128/mcb.01227-08.
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ABSTRACT The intracellular accumulation of unfolded or misfolded proteins is believed to contribute to aging and age-related neurodegenerative diseases. However, the links between age-dependent proteotoxicity and cellular protein degradation systems remain poorly understood. Here, we show that 26S proteasome activity and abundance attenuate with age, which is associated with the impaired assembly of the 26S proteasome with the 19S regulatory particle (RP) and the 20S proteasome. In a genetic gain-of-function screen, we characterized Rpn11, which encodes a subunit of the 19S RP, as a suppressor of expanded polyglutamine-induced progressive neurodegeneration. Rpn11 overexpression suppressed the age-related reduction of the 26S proteasome activity, resulting in the extension of flies' life spans with suppression of the age-dependent accumulation of ubiquitinated proteins. On the other hand, the loss of function of Rpn11 caused an early onset of reduced 26S proteasome activity and a premature age-dependent accumulation of ubiquitinated proteins. It also caused a shorter life span and an enhanced neurodegenerative phenotype. Our results suggest that maintaining the 26S proteasome with age could extend the life span and suppress the age-related progression of neurodegenerative diseases.
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Wan, Wenbin, Lan Cao, Bill Kalionis, Shijin Xia, and Xiantao Tai. "Applications of Induced Pluripotent Stem Cells in Studying the Neurodegenerative Diseases." Stem Cells International 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/382530.
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Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons. Incurable neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) show dramatic rising trends particularly in the advanced age groups. However, the underlying mechanisms are not yet fully elucidated, and to date there are no biomarkers for early detection or effective treatments for the underlying causes of these diseases. Furthermore, due to species variation and differences between animal models (e.g., mouse transgenic and knockout models) of neurodegenerative diseases, substantial debate focuses on whether animal and cell culture disease models can correctly model the condition in human patients. In 2006, Yamanaka of Kyoto University first demonstrated a novel approach for the preparation of induced pluripotent stem cells (iPSCs), which displayed similar pluripotency potential to embryonic stem cells (ESCs). Currently, iPSCs studies are permeating many sectors of disease research. Patient sample-derived iPSCs can be used to construct patient-specific disease models to elucidate the pathogenic mechanisms of disease development and to test new therapeutic strategies. Accordingly, the present review will focus on recent progress in iPSC research in the modeling of neurodegenerative disorders and in the development of novel therapeutic options.
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Polymenidou, Magdalini, and Don W. Cleveland. "Prion-like spread of protein aggregates in neurodegeneration." Journal of Experimental Medicine 209, no. 5 (May 7, 2012): 889–93. http://dx.doi.org/10.1084/jem.20120741.
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Protein misfolding is common to most neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases. Recent work using animal models with intracellular α-synuclein and tau inclusions adds decisively to a growing body of evidence that misfolded protein aggregates can induce a self-perpetuating process that leads to amplification and spreading of pathological protein assemblies. When coupled with the progressive nature of neurodegeneration, recognition of such cell-to-cell aggregate spread suggests a unifying mechanism underlying the pathogenesis of these disorders.
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Chen, Dongmei, Tao Zhang, and Tae Ho Lee. "Cellular Mechanisms of Melatonin: Insight from Neurodegenerative Diseases." Biomolecules 10, no. 8 (August 7, 2020): 1158. http://dx.doi.org/10.3390/biom10081158.
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Neurodegenerative diseases are the second most common cause of death and characterized by progressive impairments in movement or mental functioning in the central or peripheral nervous system. The prevention of neurodegenerative disorders has become an emerging public health challenge for our society. Melatonin, a pineal hormone, has various physiological functions in the brain, including regulating circadian rhythms, clearing free radicals, inhibiting biomolecular oxidation, and suppressing neuroinflammation. Cumulative evidence indicates that melatonin has a wide range of neuroprotective roles by regulating pathophysiological mechanisms and signaling pathways. Moreover, melatonin levels are decreased in patients with neurodegenerative diseases. In this review, we summarize current knowledge on the regulation, molecular mechanisms and biological functions of melatonin in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, vascular dementia and multiple sclerosis. We also discuss the clinical application of melatonin in neurodegenerative disorders. This information will lead to a better understanding of the regulation of melatonin in the brain and provide therapeutic options for the treatment of various neurodegenerative diseases.
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da Cruz, Alexandre Bettencourt, Martin Schwärzel, Sabine Schulze, Mahtab Niyyati, Martin Heisenberg, and Doris Kretzschmar. "Disruption of the MAP1B-related Protein FUTSCH Leads to Changes in the Neuronal Cytoskeleton, Axonal Transport Defects, and Progressive Neurodegeneration in Drosophila." Molecular Biology of the Cell 16, no. 5 (May 2005): 2433–42. http://dx.doi.org/10.1091/mbc.e04-11-1004.
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The elaboration of neuronal axons and dendrites is dependent on a functional cytoskeleton. Cytoskeletal components have been shown to play a major role in the maintenance of the nervous system through adulthood, and changes in neurofilaments and microtubule-associated proteins (MAPs) have been linked to a variety of neurodegenerative diseases. Here we show that Futsch, the fly homolog of MAP1B, is involved in progressive neurodegeneration. Although Futsch is widely expressed throughout the CNS, degeneration in futscholk primarily occurs in the olfactory system and mushroom bodies. Consistent with the predicted function of Futsch, we find abnormalities in the microtubule network and defects in axonal transport. Degeneration in the adult brain is preceded by learning deficits, revealing a neuronal dysfunction before detectable levels of cell death. Futsch is negatively regulated by the Drosophila Fragile X mental retardation gene, and a mutation in this gene delays the onset of neurodegeneration in futscholk. A similar effect is obtained by expression of either fly or bovine tau, suggesting a certain degree of functional redundancy of MAPs. The futscholk mutants exhibit several characteristics of human neurodegenerative diseases, providing an opportunity to study the role of MAPs in progressive neurodegeneration within an experimentally accessible, in vivo model system.
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Ruffini, Nicolas, Susanne Klingenberg, Susann Schweiger, and Susanne Gerber. "Common Factors in Neurodegeneration: A Meta-Study Revealing Shared Patterns on a Multi-Omics Scale." Cells 9, no. 12 (December 8, 2020): 2642. http://dx.doi.org/10.3390/cells9122642.
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Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) are heterogeneous, progressive diseases with frequently overlapping symptoms characterized by a loss of neurons. Studies have suggested relations between neurodegenerative diseases for many years (e.g., regarding the aggregation of toxic proteins or triggering endogenous cell death pathways). We gathered publicly available genomic, transcriptomic, and proteomic data from 177 studies and more than one million patients to detect shared genetic patterns between the neurodegenerative diseases on three analyzed omics-layers. The results show a remarkably high number of shared differentially expressed genes between the transcriptomic and proteomic levels for all conditions, while showing a significant relation between genomic and proteomic data between AD and PD and AD and ALS. We identified a set of 139 genes being differentially expressed in several transcriptomic experiments of all four diseases. These 139 genes showed overrepresented gene ontology (GO) Terms involved in the development of neurodegeneration, such as response to heat and hypoxia, positive regulation of cytokines and angiogenesis, and RNA catabolic process. Furthermore, the four analyzed neurodegenerative diseases (NDDs) were clustered by their mean direction of regulation throughout all transcriptomic studies for this set of 139 genes, with the closest relation regarding this common gene set seen between AD and HD. GO-Term and pathway analysis of the proteomic overlap led to biological processes (BPs), related to protein folding and humoral immune response. Taken together, we could confirm the existence of many relations between Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis on transcriptomic and proteomic levels by analyzing the pathways and GO-Terms arising in these intersections. The significance of the connection and the striking relation of the results to processes leading to neurodegeneration between the transcriptomic and proteomic data for all four analyzed neurodegenerative diseases showed that exploring many studies simultaneously, including multiple omics-layers of different neurodegenerative diseases simultaneously, holds new relevant insights that do not emerge from analyzing these data separately. Furthermore, the results shed light on processes like the humoral immune response that have previously been described only for certain diseases. Our data therefore suggest human patients with neurodegenerative diseases should be addressed as complex biological systems by integrating multiple underlying data sources.
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Lee, Banseok, Myeongcheol Shin, Youngjae Park, So-Yoon Won, and Kyoung Sang Cho. "Physical Exercise-Induced Myokines in Neurodegenerative Diseases." International Journal of Molecular Sciences 22, no. 11 (May 28, 2021): 5795. http://dx.doi.org/10.3390/ijms22115795.
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Neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), are disorders characterized by progressive degeneration of the nervous system. Currently, there is no disease-modifying treatments for most NDs. Meanwhile, numerous studies conducted on human and animal models over the past decades have showed that exercises had beneficial effects on NDs. Inter-tissue communication by myokine, a peptide produced and secreted by skeletal muscles during exercise, is thought to be an important underlying mechanism for the advantages. Here, we reviewed studies about the effects of myokines regulated by exercise on NDs and their mechanisms. Myokines could exert beneficial effects on NDs through a variety of regulatory mechanisms, including cell survival, neurogenesis, neuroinflammation, proteostasis, oxidative stress, and protein modification. Studies on exercise-induced myokines are expected to provide a novel strategy for treating NDs, for which there are no adequate treatments nowadays. To date, only a few myokines have been investigated for their effects on NDs and studies on mechanisms involved in them are in their infancy. Therefore, future studies are needed to discover more myokines and test their effects on NDs.
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Kovacs, Gabor G. "Molecular pathology of neurodegenerative diseases: principles and practice." Journal of Clinical Pathology 72, no. 11 (August 8, 2019): 725–35. http://dx.doi.org/10.1136/jclinpath-2019-205952.
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Neurodegenerative diseases are characterised by selective dysfunction and progressive loss of synapses and neurons associated with pathologically altered proteins that deposit primarily in the human brain and spinal cord. Recent discoveries have identified a spectrum of distinct immunohistochemically and biochemically detectable proteins, which serve as a basis for protein-based disease classification. Diagnostic criteria have been updated and disease staging procedures have been proposed. These are based on novel concepts which recognise that (1) most of these proteins follow a sequential distribution pattern in the brain suggesting a seeding mechanism and cell-to-cell propagation; (2) some of the neurodegeneration-associated proteins can be detected in peripheral organs; and (3) concomitant presence of neurodegeneration-associated proteins is more the rule than the exception. These concepts, together with the fact that the clinical symptoms do not unequivocally reflect the molecular pathological background, place the neuropathological examination at the centre of requirements for an accurate diagnosis. The need for quality control in biomarker development, clinical and neuroimaging studies, and evaluation of therapy trials, as well as an increasing demand for the general public to better understand human brain disorders, underlines the importance for a renaissance of postmortem neuropathological studies at this time. This review summarises recent advances in neuropathological diagnosis and reports novel aspects of relevance for general pathological practice.