Autophagy in microglia degrades extracellular ?-amyloid fibrils and regulates the NLRP3 inflammasome.

Accumulation of ?-amyloid (A?) and resultant inflammation are critical pathological features of Alzheimer disease (AD). Microglia, a primary immune cell in brain, ingests and degrades extracellular A? fibrils via the lysosomal system. Autophagy is a catabolic process that degrades native cellular components, however, the role of autophagy in A? degradation ...
by microglia and its effects on AD are unknown. Here we demonstrate a novel role for autophagy in the clearance of extracellular A? fibrils by microglia and in the regulation of the A?-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? 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.
Mesh Terms:
AMP-Activated Protein Kinases, Adaptor Proteins, Signal Transducing, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Animals, Autophagy, Autophagy-Related Protein 7, Carrier Proteins, Cell Line, Extracellular Space, Eye Proteins, Female, Heat-Shock Proteins, Humans, Inflammasomes, Inflammation, Integrases, Male, Mice, Microglia, Microtubule-Associated Proteins, Models, Biological, NLR Family, Pyrin Domain-Containing 3 Protein, Neurons, Proteolysis, Sequestosome-1 Protein, Transcription Factor TFIIIA
Autophagy
Date: Oct. 01, 2014
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