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学科主题临床医学
Mice deficient in Epg5 exhibit selective neuronal vulnerability to degeneration
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
2013-03-18
DOI10.1083/jcb.201211014
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
WOS记录号WOS:000316255400007
引用统计
被引频次:38[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/63368
专题北京大学第三临床医学院_神经内科
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
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GB/T 7714
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.
APA Zhao, Hongyu.,Zhao, Yan G..,Wang, Xingwei.,Xu, Lanjun.,Miao, Lin.,...&Zhang, Hong.(2013).Mice deficient in Epg5 exhibit selective neuronal vulnerability to degeneration.JOURNAL OF CELL BIOLOGY,200(6),731-741.
MLA Zhao, Hongyu,et al."Mice deficient in Epg5 exhibit selective neuronal vulnerability to degeneration".JOURNAL OF CELL BIOLOGY 200.6(2013):731-741.
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