期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 5, 页码 1590-1595出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2964-15.2016
关键词
abeta; AMPA receptor; endocytosis; Nedd4-1; ubiquitin
资金
- National Institutes of Health [T32 NS007220, NS060847, T32 AG00216]
- National Science Foundation
- Center for Systems Biology [P50-GMO85764]
Alzheimer's disease (AD) is a neurodegenerative disease in which patients experience progressive cognitive decline. A wealth of evidence suggests that this cognitive impairment results from synaptic dysfunction in affected brain regions caused by cleavage of amyloid precursor protein into the pathogenic peptide amyloid-beta (A beta). Specifically, it has been shown that A beta decreases surface AMPARs, dendritic spine density, and synaptic strength, and also alters synaptic plasticity. The precise molecular mechanisms by which this occurs remain unclear. Here we demonstrate a role for ubiquitination in A beta-induced synaptic dysfunction in cultured rat neurons. We find that A beta promotes the ubiquitination of AMPARs, as well as the redistribution and recruitment of Nedd4-1, a HECT E3 ubiquitin ligase we previously demonstrated to target AMPARs for ubiquitination and degradation. Strikingly, we show that Nedd4-1 is required for A beta-induced reductions in surface AMPARs, synaptic strength, and dendritic spine density. Our findings, therefore, indicate an important role for Nedd4-1 and ubiquitin in the synaptic alterations induced by A beta.
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