Endosome function and dysfunction in Alzheimer's disease and other neurodegenerative diseases

被引:296
作者
Nixon, RA [1 ]
机构
[1] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA
[2] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA
[3] Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA
关键词
endosomes; lysosomes; amyloid; Huntington disease; AM APP;
D O I
10.1016/j.neurobiolaging.2004.09.018
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Endocytosis is universally important in cell function. In the brain, the roles of endosomes are relatively more complex due to the unique polar morphology of neurons and specialized needs for inter-cellular communication. New evidence shows that endosome function is altered in a surprising range of neurodegenerative disorders, including in several inherited neurologic disorders where the causative mutations occur in genes that regulate endosome function. In Alzheimer's disease (AD), endosome abnormalities are among the earliest neuropathologic features to develop and have now been closely linked to genetic risk factors for AD, including APP triplication in Trisomy 21 (Down syndrome, DS) and ApoE4 genotype in sporadic AD. Recent findings on endosome regulation and developmental and late-onset neurodegenerative disease disorders are beginning to reveal how endocytic pathway impairment may lead to neuronal dysfunction and cell death in these disorders and may also promote amyloidogenesis in AD. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:373 / 382
页数:10
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