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

Autophagy 2014 Oct 22;10(10):1761-75. Epub 2014 Jul 22.

Alzheimer Disease Experts Lab (ADEL); Asan Institute of Life Sciences; Asan Medical Center; University of Ulsan College of Medicine; Seoul, Korea; Department of Anatomy and Cell Biology; University of Ulsan College of Medicine; Seoul, Korea; Bio-Medical Institute of Technology (BMIT); University of Ulsan College of Medicine; Seoul, Korea; Cell Dysfunction Research Center (CDRC); University of Ulsan College of Medicine; Seoul, Korea.

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 atg7 knockout 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.

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http://dx.doi.org/10.4161/auto.29647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4198361PMC
October 2014
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References

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Giménez-Xavier P et al.
Int J Mol Med 2008

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