期刊
JOURNAL OF CELL BIOLOGY
卷 171, 期 1, 页码 87-98出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200505082
关键词
-
类别
资金
- NIA NIH HHS [R01 AG021904, AG021904, P01 AG017617, AG17617-05, R37 AG021904] Funding Source: Medline
Macroautophagy, which is a lysosomal pathway for the turnover of organelles and long-lived proteins, is a key determinant of cell survival and longevity. In this study, we show that neuronal macroautophagy is induced early in Alzheimer's disease ( AD) and before beta-amyloid (A beta) deposits extracellularly in the presenilin ( PS) 1/A beta precursor protein (APP) mouse model of beta-amyloidosis. Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate markedly in dystrophic dendrites, implying an impaired maturation of AVs to M lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of intracellular A beta. Purified AVs contain APP and beta-cleaved APP and are highly enriched in PS1, nicastrin, and PS-dependent gamma-secretase activity. Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by modulating mammalian target of rapamycin kinase elicits parallel changes in AV proliferation and A beta production. Our results, therefore, link beta-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据