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学科主题: 临床医学
题名:
Mice deficient in Epg5 exhibit selective neuronal vulnerability to degeneration
作者: Zhao, Hongyu1,4; Zhao, Yan G.2,4; Wang, Xingwei2,4; Xu, Lanjun2,4; Miao, Lin4; Feng, Du5; Chen, Quan3; Kovacs, Attila L.6; Fan, Dongsheng7; Zhang, Hong2
刊名: JOURNAL OF CELL BIOLOGY
发表日期: 2013-03-18
DOI: 10.1083/jcb.201211014
卷: 200, 期:6, 页:731-741
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: AMYOTROPHIC-LATERAL-SCLEROSIS ; NEURODEGENERATIVE DISEASE ; AUTOPHAGOSOME FORMATION ; MUTATIONS ; ALS ; PROTEINS ; VCP
英文摘要:

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.

语种: 英语
所属项目编号: 2013CB910100 ; 2011CB910100 ; OTKA K75843
项目资助者: National Basic Research Program of China ; Hungarian Scientific Research Funds ; Howard Hughes Medical Institute
WOS记录号: WOS:000316255400007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63368
Appears in Collections:北京大学第三临床医学院_神经内科_期刊论文

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作者单位: 1.China Agr Univ, Coll Life Sci, Beijing 100083, Peoples R China
2.Chinese Acad Sci, Inst Biophys, State Key Lab Biomacromol, Beijing 100101, Peoples R China
3.Chinese Acad Sci, Inst Zool, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100101, Peoples R China
4.Natl Inst Biol Sci, Beijing 102206, Peoples R China
5.Guangdong Med Coll, Affiliated Hosp, Inst Neurol, Zhanjiang 524001, Peoples R China
6.Eotvos Lorand Univ, Dept Anat Cell & Dev Biol, H-1117 Budapest, Hungary
7.Peking Univ, Hosp 3, Dept Neurol, Beijing 100191, Peoples R China

Recommended Citation:
Zhao, Hongyu,Zhao, Yan G.,Wang, Xingwei,et al. Mice deficient in Epg5 exhibit selective neuronal vulnerability to degeneration[J]. JOURNAL OF CELL BIOLOGY,2013,200(6):731-741.
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