期刊
AUTOPHAGY
卷 10, 期 10, 页码 1761-1775出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/auto.29647
关键词
Alzheimer disease; beta-amyloid; autophagy; microglia; NLRP3
类别
资金
- National Research Foundation of Korea [2008-0062286]
- Ministry of Education, Science, and Technology [2012R1A1A1039173]
- Asan Institute for Life Sciences, Seoul, Korea [2012-522]
- National Research Foundation of Korea [2012R1A1A1039173, 2008-0062286] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Accumulation of beta-amyloid (A beta) and resultant inflammation are critical pathological features of Alzheimer disease (AD). Microglia, a primary immune cell in brain, ingests and degrades extracellular A beta fibrils via the lysosomal system. Autophagy is a catabolic process that degrades native cellular components, however, the role of autophagy in A beta degradation by microglia and its effects on AD are unknown. Here we demonstrate a novel role for autophagy in the clearance of extracellular A beta fibrils by microglia and in the regulation of the A beta-induced NLRP3 (NLR family, pyrin domain containing 3) inflammasome using microglia specific atg7 knockout mice and cell cultures. We found in microglial cultures that A beta interacts with MAP1LC3B-II via OPTN/optineurin and is degraded by an autophagic process mediated by the PRKAA1 pathway. We anticipate that enhancing microglial autophagy may be a promising new therapeutic strategy for 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