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Dissertations / Theses on the topic 'Glucosylceramidase'

Author: Grafiati

Published: 4 June 2021

Last updated: 7 July 2024

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1

Lecourt, Séverine. "Mécanismes cellulaires et moléculaires régissant la biologie des cellules souches médullaires dans la maladie de Gaucher de type 1." Paris 7, 2011. http://www.theses.fr/2011PA077122.

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La maladie de Gaucher est une maladie génétique rare liée à des mutations dans le gène codant pour la glucocérébrosidase (GBA). Dans la maladie de Gaucher de type 1, l'accumulation de glucosylcéramide dans les lysosomes des cellules affectées provoque des manifestations cliniques hétérogènes incluant des atteintes viscérales, hématologiques et osseuses dont les mécanismes physiopathologiques sont encore mal connus à ce jour. L'objectif de ce travail de thèse a été d'étudier la biologie fonctionnelle de populations cellulaires non encore étudiées dans le contexte de cette pathologie, en particu

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2

Spitz, Mariana. "Mutações da glicocerebrosidade em pacientes com doença de Parkinson." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5138/tde-05022007-123329/.

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Introdução: A doença de Parkinson é uma enfermidade neurodegenerativa decorrente da perda de neurônios dopaminérgicos na substância negra, principalmente, e em outras regiões cerebrais. Caracteriza-se clinicamente por tremor, rigidez, bradicinesia e instabilidade postural. O tratamento é sintomático e consiste essencialmente na reposição da dopamina deficiente. A etiologia da doença de Parkinson ainda não é conhecida, mas os recentes avanços da Neurologia trouxeram novos conhecimentos acerca dos mecanismos fisiopatológicos envolvidos. Disfunção mitocondrial, estresse oxidativo e degradação de

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3

Melser, Su. "Implication du Glucosylceramide dans la voie sécretoire des plantes." Thesis, Bordeaux 2, 2009. http://www.theses.fr/2009BOR21637/document.

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Le rôle des lipides comme des acteurs moléculaires de la voie sécrétoire des plantes n'est pas encore complètement élucidé. Le Glucosylceramide (GlcCer) est synthétisé par la Glucosylceramide synthase (GCS) chez les plantes et constitue un des sphingolipides complexes clé dans les membranes, mais on connaît peu les exigences cellulaires pour le GlcCer. Cette étude repose sur le blocage de la biosynthèse de GlcCer, par l'utilisation d'inhibiteurs chez le tabac et l’arabidopsis, et la production de mutants d'Arabidopsis, pour déterminer l'impact de la biosynthèse du GlcCer sur la dynamique endom

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4

Dupre, Tess V., Mark A. Doll, Parag P. Shah, et al. "Inhibiting glucosylceramide synthase exacerbates cisplatin-induced acute kidney injury." AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017. http://hdl.handle.net/10150/624924.

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Acute kidney injury (AKI), resulting from chemotherapeutic agents such as cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI involves apoptotic and necrotic cell death, pathways regulated by sphingolipids such as ceramide and glucosylceramide. Results from this study indicate that C57BL/6J mice treated with cisplatin had increased ceramide and hexosylceramide levels in the renal cortex 72 h following cisplatin treatment. Pretreatment of mice with inhibitors of acid sphingomyelinase and de novo ceramide synthesis (amitriptyline and myriocin, respectively) prevented

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5

Breen, Imogen Zofia. "Glucosylceramide metabolism : from 3D structure to the development of selective chemical probes." Thesis, University of York, 2017. http://etheses.whiterose.ac.uk/19181/.

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Gaucher's disease, the most prevalent of the lysosomal storage disorders, is caused by insufficient lysosomal glucocerebrosidase (GBA1) activity. This is the result of point mutations in the encoding gene, GBA1. The consequence of this reduction in activity is an accumulation of GBA1's substrate, glucosylceramide, in the lysosomes, leading to the various pathologies of Gaucher’s disease. Treatment approaches for Gaucher's disease range include enzyme replacement therapy, substrate reduction therapy and the use of small molecules to stabilise mutant forms of the enzyme – pharmacological chapero

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6

Raju, Diana Nancy [Verfasser]. "Non-lysosomal accumulation of glucosylceramide alters cytoskeletal dynamics causing globozoospermia / Diana Nancy Raju." Bonn : Universitäts- und Landesbibliothek Bonn, 2015. http://d-nb.info/107728974X/34.

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7

Bonte, Marie-Amandine. "Impact de l'inhibition de l'activité de la glucocérébrosidase sur les évènements moléculaires associés à la maladie de Parkinson." Electronic Thesis or Diss., Université de Lille (2022-....), 2024. https://pepite-depot.univ-lille.fr/ToutIDP/EDBSL/2024/2024ULILS012.pdf.

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La maladie de Parkinson est une maladie neurodégénérative progressive caractérisée par la perte de neurones dopaminergiques, l’accumulation de lésions intraneuronales nommées corps de Lewy et l’accumulation en fer au niveau de la substance noire. Des mutations touchant le gène GBA, codant pour la glucocérébrosidase lysosomale, ont été associées au risque de survenue de la maladie de Parkinson. La glucocérébrosidase est une enzyme impliquée dans l’hydrolyse des glucosylcéramides en glucose et céramides modifiant ainsi la composition lipidique membranaire. Son activité enzymatique est réduite da

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8

Amen, Nicole [Verfasser], and Peter [Akademischer Betreuer] Angel. "The role of Glucosylceramides in Keratinocyte Differentiation and Epidermal Barrier Function / Nicole Amen ; Betreuer: Peter Angel." Heidelberg : Universitätsbibliothek Heidelberg, 2013. http://d-nb.info/1177380560/34.

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9

Singh, Priyanka. "The Role of Neutral Sphingolipids in the Pathogenesis of Parkinson Disease and Dementia with Lewy Bodies." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/24029.

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The molecular mechanisms underlying the association between mutations in GBA1 and risk of developing the ‘synucleinopathy’ disorders Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) remain elusive. To better understand the precise molecular cascade that connects GBA1 mutations with α-synuclein dysregulation, a modified lipid extraction and HPTLC protocol was optimized to detect changes in levels of neutral sphingolipids (SLs) from neural cells and tissue expressing wild-type (WT) GBA1, mutant GBA1, or both. We demonstrate that mutant GBA1 does not confer a dominant-negative effect

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10

Ito, Mitsuru. "Possible role of ceramide as an indicator of chemoresistance : decrease of the ceramide content via activation of glucosylceramide synthase and sphingomyelin synthase in chemoresistant leukemia." Kyoto University, 2003. http://hdl.handle.net/2433/148774.

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11

Lindholm, Ellinor. "Production of gangliosidebiosynthetic membrane enzymes for biochemical and functionalstudies : Expression, purification and crystallizationoptimization of Thermococcus onnurineus Dolicho l-phosphate mannose synthase, Homosapiens and Branchiostoma floridae Glucosylceramide synthase." Thesis, KTH, Skolan för kemi, bioteknologi och hälsa (CBH), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-230765.

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Glycolipids play important roles in the biology of prokaryotes and eukaryotes, including humans, and although theyare found on the cell-membrane surface of all eukaryotic cells, not much is known about their biosynthesis. The aim ofthis project was to characterize two enzymes: glucosylceramide synthase (GCS) which is involved in the biosynthesisof glycolipids such as gangliosides that are abundant in the membranes of nerve cells; and dolicholphosphate mannosesynthase (DPMS), involved in the synthesis precursor for protein glycosylation. Both GCS and DPMS have beenshown play a role in cancer as

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12

Liu, Ying. "Regulation of ceramide and its metabolites: biosynthesis and; in situ sphingolipid analysis." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/33918.

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Sphingolipids are found in essentially all animals, plants and fungi, and some prokaryotic organisms and viruses. Sphingolipids function as structural components of membranes, lipoproteins, and as cell signaling modulators and mediators. To complicate matters further, sphingolipids often vary in type in different regions of tissues, and even in single cells, the subcellular localization of sphingolipids and their metabolic enzymes, transport proteins and targets may influence their functions. It is important to study sphingolipids spatial distribution within living organisms to understand how

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13

Aumer, Thomas. "Étude du mécanisme d'action d'un peptide antifongique de la famille des héliomicines pour contrôler le champignon phytopathogène Botrytis cinerea." Thesis, Université Grenoble Alpes (ComUE), 2019. https://thares.univ-grenoble-alpes.fr/2019GREAV038.pdf.

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Les champignons phytopathogènes sont la principale cause de maladies chez les plantes cultivées. Botrytis cinerea est un champignon nécrotrophe, responsable de la pourriture grise, ciblant de nombreuses cultures d’intérêt agronomique (tomate, vigne, fraise). La lutte contre ce pathogène intègre la recherche de nouvelles solutions antifongiques dérivées de molécules naturelles telles que les peptides antimicrobiens (PAMs). Le peptide ETD151 est un PAM exclusivement antifongique optimisé à partir de l’héliomicine, une défensine d’insecte isolée chez le papillon Heliothis virescens. Ce petit pept

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14

Astudillo, Leonardo. "Rôle des sphingolipides dans la cancérogenèse : l'exemple de la maladie de Gaucher." Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30401.

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Les sphingolipides représentent une classe majeure de lipides qui sont des constituants de toutes les cellules eucaryotes. Ils sont des effecteurs bioactifs impliqués dans les fonctions clés cellulaires comme la différenciation, la prolifération, la motilité, l'apoptose et la sénescence. De plus, leur rôle dans le cancer est maintenant bien établi pour de nombreux sphingolipides. La maladie de Gaucher (MG) est une lipidose héréditaire, à transmission autosomique récessive, due à un déficit enzymatique en glucocérébrosidase (béta-glucosidase acide, codée par le gène GBA1). Cette enzyme est une

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15

Πολυβίου, Σταύρος. "Μελέτη της γονιδιακής μεταφοράς του γονιδίου της γλυκοκερεβροσιδάσης με ιικά οχήματα σε προγονικά αιμοποιητικά κύτταρα του ανθρώπου". Thesis, 2011. http://hdl.handle.net/10889/5667.

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Η ποσοτική ή ποιοτική ανεπάρκεια του λυσοσωματικού ενζύμου γλυκοκερεβροσιδάση οδηγεί στην παθολογία της νόσου Gaucher με κεντρικό το ρόλο της συσσώρευσης του υποστρώματός της, του γλυκοκερεβροσιδίου, στα μακροφάγα. Για περισσότερες από δύο δεκαετίες χρησιμοποιούνται γ-ρετροϊικά οχήματα στην ερευνητική προσέγγιση της διόρθωσης του ελλείμματος μέσω γονιδιακής μεταφοράς του γονιδίου της γλυκοκερεβροσιδάσης. Όπως έχει αναδειχθεί και σε κλινικό επίπεδο, είναι επιτακτική η ανάγκη για το σχεδιασμό γ ρετροϊικών οχημάτων, τα οποία θα είναι όχι μόνο αποτελεσματικά αλλά και ασφαλή, με κύριο στόχο τον περ

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16

Piontkivska, Daryna. "Unravelling how the biosynthesis of sphingolipids impacts stress responses in Aspergillus nidulans." Master's thesis, 2017. http://hdl.handle.net/10362/79293.

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"For the past years filamentous fungi have been emerging as critical human-pathogens and have been increasingly provoking deadly invasive infections. The currently available antifungal drugs are inadequate to fight this global threat and the discovery of new antifungal targets are urgently needed. In this context, fungal sphingolipids have come up as potential targets for the development of new antifungal agents; however, knowledge on sphingolipid biosynthetic pathways in filamentous fungi, such as Aspergillus nidulans, is still rather limited. Previous observations demonstrated that some ioni

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17

Varela, Ana Raquel Pinto 1985. "The link between altered glucosylceramide composition and membrane properties : from membrane biophysics to gaucher disease." Doctoral thesis, 2015. http://hdl.handle.net/10451/22970.

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Tese de doutoramento, Farmácia (Tecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2015<br>Lipids are one of the most abundant molecules in a cell and are involved in the regulation of cell events. One of the mechanisms by which lipids control cell signaling is by altering membrane biophysical properties. Therefore, the biophysical properties of several lipids have been thoroughly characterized. However, some bioactive lipids like glucosylceramide (GlcCer) still have their properties poorly studied. GlcCer is a lipid involved in several cell processes. A deregulation in i

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18

Illner, Jan. "Lysosomální dědičná onemocnění: patobiochemie Gaucherovy choroby." Master's thesis, 2011. http://www.nusl.cz/ntk/nusl-297600.

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Gaucher disease is one of the lysosomal storage disorders belonging to inherited defects of catabolism of sphingolipids. These defects are caused by mutation in genes of sphingolipid hydrolases or their protein activators. Subsequent storage of non-degraded sphingolipids leads to severe clinical phenotypes in patients. Gaucher disease is caused by deficiency of lysosomal β-glucocerebrosidase (GBA1) activity. Non-degraded glycosphingolipids are glucosylceramide (GlcCer) and glucosylpsychosine (lyso-GlcCer). Accumulation of these glycosphingolipids is related to Gaucher cells which are derived f

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19

Duarte, André Alexandre Rodrigues Besouro. "Immune system role on gaucher disease." Master's thesis, 2013. http://hdl.handle.net/10451/36736.

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Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2014<br>The Gaucher Disease (GD) is the most prevalent lysosomal illness in humans and it is caused by the deficiency in the enzyme Glucosylceramidase (GlcCerase) or β-D-Glucosyl-N-Acylsphingosine-Glucohydrolase. The symptoms result from the accumulation of a sphingolipid, Glucosylceramide (GlcCer), in phagocytic cells which will gather in organs such as the spleen, liver and bone obstructing its vessels. Some recent articles indicate that, in addition to the classic knowledge about thi

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20

Gallala, Hichem D. [Verfasser]. "Die Biogenese der Haut : Etablierung von mRNA-Expressionsprofilen von proliferierenden und differenzierenden Keratinozyten unter Einfluss von Stickstoff-Monoxid und Untersuchung einer Glucosylceramide-Synthase defizienten Maus / vorgelegt von Hichem D. Gallala." 2007. http://d-nb.info/982875304/34.

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21

Kamani, Mustafa. "Novel Intrinsic and Extrinsic Approaches to Selectively Regulate Glycosphingolipid Metabolism." Thesis, 2013. http://hdl.handle.net/1807/35860.

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Glycosphingolipid (GSL) metabolism is a complex process involving proteins and enzymes at distinct locations within the cell. Mammalian GSLs are typically based on glucose or galactose, forming glucosylceramide (GlcCer) and galactosylceramide (GalCer). Most GSLs are derived from GlcCer, which is synthesized on the cytosolic leaflet of the Golgi, while all subsequent GSLs are synthesized on the lumenal side. We have utilized both pharamacological and genetic manipulation approaches to selectively regulate GSL metabolism and better understand its mechanistic details. We have developed analog

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