دورية أكاديمية
Mice deficient in Epg5 exhibit selective neuronal vulnerability to degeneration
| العنوان: | Mice deficient in Epg5 exhibit selective neuronal vulnerability to degeneration |
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| المؤلفون: | Zhao, HY, Zhao, YG, Wang, XW, Xu, LJ, Miao, L, Feng, D, Chen, Q, Kovacs, AL, Fan, DS, Zhang, H |
| سنة النشر: | 2013 |
| المجموعة: | Eötvös Loránd University: ELTE Digital Institutional Repository (EDIT) / Eötvös Loránd Tudományegyetem |
| الوصف: | The molecular mechanism underlying the selective vulnerability of certain neuronal populations associated with neurodegenerative diseases remains poorly understood. Basal autophagy is important for maintaining axonal homeostasis and preventing neurodegeneration. In this paper, we demonstrate that mice deficient in the metazoan-specific autophagy gene Epg5/epg-5 exhibit selective damage of cortical layer 5 pyramidal neurons and spinal cord motor neurons. Pathologically, Epg5 knockout mice suffered muscle denervation, myofiber atrophy, late-onset progressive hindquarter paralysis, and dramatically reduced survival, recapitulating key features of amyotrophic lateral sclerosis (ALS). Epg5 deficiency impaired autophagic flux by blocking the maturation of autophagosomes into degradative autolysosomes, leading to accumulation of p62 aggregates and ubiquitin-positive inclusions in neurons and glial cells. Epg5 knockdown also impaired endocytic trafficking. Our study establishes Epg5-deficient mice as a model for investigating the pathogenesis of ALS and indicates that dysfunction of the autophagic-endolysosomal system causes selective damage of neurons associated with neurodegenerative diseases. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | http://hdl.handle.net/10831/91288Test; elte:000316255400007; elte:84876308090; elte:2282961; elte:6; elte:J CELL BIOL; elte:JOURNAL OF CELL BIOLOGY; elte:200; elte:23479740; elte:10089076; LOMS: https://edit.elte.hu/xmlui/bitstream/10831/91288/1/2282961.pdfTest |
| DOI: | 10.1083/jcb.201211014 |
| الإتاحة: | https://doi.org/10.1083/jcb.201211014Test http://hdl.handle.net/10831/91288Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.68143047 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1083/jcb.201211014 |
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