Glial contribution to cyclodextrin-mediated reversal of cholesterol accumulation in murine NPC1-deficient neurons in vivo
| العنوان: | Glial contribution to cyclodextrin-mediated reversal of cholesterol accumulation in murine NPC1-deficient neurons in vivo |
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| المؤلفون: | Amélie Barthelemy, Eugeniu Vasile, Frank W. Pfrieger, Sophie Reibel, Tom Houben, Michael Reber, Martine Perraut, Izabela-Cristina Stancu, Valentina Pallottini, Valérie Demais |
| المساهمون: | Institut National de l'Environnement Industriel et des Risques (INERIS), Department of Molecular Genetics [Maastricht, The Netherlands], Maastricht University [The Netherlands], Centre de Neurochimie, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Barthelemy, A., Demais, V., Stancu, I. -C., Vasile, E., Houben, T., Reber, M., Pallottini, V., Perraut, M., Reibel, S., Pfrieger, F. W. |
| المصدر: | Neurobiology of Disease Neurobiology of Disease, Elsevier, 2021, 158, ⟨10.1016/j.nbd.2021.105469⟩ Neurobiology of Disease, Vol 158, Iss, Pp 105469-(2021) Neurobiology of Disease, 158:105469. Elsevier Science |
| بيانات النشر: | HAL CCSD, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, NIEMANN-PICK-DISEASE, LYSOSOMAL CHOLESTEROL, Metal Nanoparticles, UNESTERIFIED CHOLESTEROL, Amacrine cells, Mice, 0302 clinical medicine, Muller cells, BRAIN, Inclusion Bodies, Neurons, Mice, Inbred BALB C, 0303 health sciences, Microglia, BETA-CYCLODEXTRINS, Chemistry, Neutrophil granulocytes, Ganglion cells, MOUSE MODEL, Lysosome, 3. Good health, Cell biology, Cholesterol, medicine.anatomical_structure, Neurology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Astrocyte, Neuroglia, Intracellular, RC321-571, Ganglion cell, Central nervous system, Neurosciences. Biological psychiatry. Neuropsychiatry, Retina, LIPOPROTEIN-DERIVED CHOLESTEROL, 03 medical and health sciences, Niemann-Pick C1 Protein, In vivo, medicine, Extracellular, Cyclodextrin, Animals, Inherited metabolic disease, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, INTRACELLULAR-TRANSPORT, 030304 developmental biology, Cyclodextrins, Müller cell, Lipid Metabolism, NPC1, Mechanism of action, Astrocytes, Gold, C DISEASE, Intravitreal, 030217 neurology & neurosurgery, Amacrine cell |
| الوصف: | International audience; Niemann-Pick type C disease is a rare and fatal lysosomal storage disorder presenting severe neurovisceral symptoms. Disease-causing mutations in genes encoding either NPC1 or NPC2 protein provoke accumulation of cholesterol and other lipids in specific structures of the endosomal-lysosomal system and degeneration of specific cells, notably neurons in the central nervous system (CNS). 2-hydroxypropyl-beta-cyclodextrin (CD) emerged as potential therapeutic approach based on animal studies and clinical data, but the mechanism of action in neurons has remained unclear. To address this topic in vivo, we took advantage of the retina as highly accessible part of the CNS and intravitreal injections as mode of drug administration. Coupling CD to gold nanoparticles allowed us to trace its intracellular location. We report that CD enters the endosomal-lysosomal system of neurons in vivo and enables the release of lipid-laden lamellar inclusions, which are then removed from the extracellular space by specific types of glial cells. Our data suggest that CD induces a concerted action of neurons and glial cells to restore lipid homeostasis in the central nervous system. |
| اللغة: | English |
| تدمد: | 0969-9961 1095-953X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6ab9d03aa4ffafcc801682d15d00b054Test https://hal.archives-ouvertes.fr/hal-03436977/file/1-s2.0-S0969996121002187-main.pdfTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6ab9d03aa4ffafcc801682d15d00b054 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09699961 1095953X |
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