Cited by 396Autophagy in Disease and TherapyAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

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

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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, Yoon, Seung-Yong·2014·Autophagy

DOI 10.4161/auto.29647PMC PMC4198361

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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 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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Authors: Cho, M.-H., Cho, K., Kang, H.-J., Jeon, E.-Y., Kim, H.-S., Kwon, H.-J., Kim, H.-M., Kim, D.-H., & Yoon, S.-Y.
Affiliations: Asan Medical Center (KR)
University of Ulsan (KR)
Corresponding author: Yoon, Seung-Yong
ORCID: Cho, Kwangmin
Yoon, Seung-Yong
Venue: Autophagy
Publisher: Informa UK Limited
Published: 2014-07-22
Volume: 10
Issue: 10
Pages: 1761-1775
ISSN: 1554-8627 (ISSN-L)
1554-8635
DOI: 10.4161/auto.29647
PMC: PMC4198361
OpenAlex: W2099588975
Cited by: 395
References: 47
Citations by year: 2026: 26 · 2025: 28 · 2024: 38 · 2023: 45 · 2022: 51 · 2021: 41 · 2020: 49 · 2019: 34 · 2018: 19 · 2017: 30 · 2016: 20 · 2015: 13 · 2014: 1
FWCI: 16.12
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Autophagy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Research Foundation
National Research Foundation of Korea (2008-0062286)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: microglia, amyloid-beta, Alzheimer's disease, NLRP3 inflammasome, lysosomal degradation, LC3B, PRKAA1, neuroinflammation
MeSH terms: Autophagy-Related Protein 7, NLR Family, Pyrin Domain-Containing 3 Protein, Sequestosome-1 Protein, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Autophagy, Carrier Proteins, Cell Line, Extracellular Space, Eye Proteins, Female, Heat-Shock Proteins, Humans, Inflammation, Male, Microtubule-Associated Proteins, Models, Biological, Neurons, Amyloid beta-Peptides, Microglia, Cell Cycle Proteins, Integrases, Membrane Transport Proteins, Transcription Factor TFIIIA, Adaptor Proteins, Signal Transducing, Mice, AMP-Activated Protein Kinases, Inflammasomes, Proteolysis

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

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