1. Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome
- Author
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Cho, Mi-Hyang, Cho, Kwangmin, Kang, Hoe-Jin, Jeon, Eun-Young, Kim, Hun-Sik, Kwon, Hyung-Joon, Kim, Hong-Mi, Kim, Dong-Hou, and Yoon, Seung-Yong
- Abstract
Accumulation of β-amyloid (Aβ) and resultant inflammation are critical pathological features of Alzheimer disease (AD). Microglia, a primary immune cell in brain, ingests and degrades extracellular Aβ fibrils via the lysosomal system. Autophagy is a catabolic process that degrades native cellular components, however, the role of autophagy in Aβ degradation by microglia and its effects on AD are unknown. Here we demonstrate a novel role for autophagy in the clearance of extracellular Aβ fibrils by microglia and in the regulation of the Aβ-induced NLRP3 (NLR family, pyrin domain containing 3) inflammasome using microglia specific atg7knockout mice and cell cultures. We found in microglial cultures that Aβ 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.
- Published
- 2014
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