The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Autophagy in microglia degrades extracellular β-amyloid fibrils and regulates the NLRP3 inflammasome
Open accessAbstract
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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“However, enhancing A β uptake/efflux without simultaneously improving intracellular degradative capacity may impose an additional proteostatic burden on cells [ 28, 31 ].”
From Restores Aβ Clearance by Overcoming PCSK9–LRP1 Dysregulation and TRIB3‐Mediated Autophagy Blockade in Alzheimer's Disease (2026) · cites this paper as [28]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In AD, autophagic flux is impaired, exacerbating A β deposition [ 28, 29 ].”
From Restores Aβ Clearance by Overcoming PCSK9–LRP1 Dysregulation and TRIB3‐Mediated Autophagy Blockade in Alzheimer's Disease (2026) · cites this paper as [28]
Experimental — accuracy not yet measuredIn the citing paper
“one study showed that microglial autophagy facilitates clearance of extracellular Aβ fibrils and reduces Aβ-induced NLRP3 activation (200).”
From Microglia Function in the Central Nervous System During Health and Neurodegeneration (2017) · cites this paper as [200]
In the citing paper
“microglial phagocytosis of Aβ deposits in Alzheimer disease models [430,431] requires the autophagy-related factors BECN1, ATG7 and LC3 [432,433].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [432]
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“autophagy may also enhance microglial clearance of Aβ”
From TREM2 Maintains Microglial Metabolic Fitness in Alzheimer’s Disease (2017) · cites this paper as Cho et al., 2014
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Citations
Cites
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Autophagy in immunity and inflammation
Levine, B., Mizushima, N., & Virgin, H. W. (2011) · Nature · doi:10.1038/nature09782 · Cited by 3,289
Nakahira, K., Haspel, J. A., Rathinam, V. A. K., Lee, S.-J., Dolinay, T., Lam, H. C., Englert, J. A., Rabinovitch, M., Cernadas, M., Kim, H. P., et al. (2011) · Nature Immunology · doi:10.1038/ni.1980 · Cited by 3,049
Self-citationThe AMPK signalling pathway coordinates cell growth, autophagy and metabolism
Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923
NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice
Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, A., Tzeng, T.-C., et al. (2013) · Nature · doi:10.1038/nature11729 · Cited by 2,898
PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
Geisler, S., Holmström, K. M., Skujat, D., Fiesel, F. C., Rothfuss, O. C., Kahle, P. J., & Springer, W. (2010) · Nature Cell Biology · doi:10.1038/ncb2012 · Cited by 2,835
How to Interpret LC3 Immunoblotting
Mizushima, N., & Yoshimori, T. (2007) · Autophagy · doi:10.4161/auto.4600 · Cited by 2,595 · cited 2×
“bBraak stage based on neurofibrillary tangles was 5 or 6 in aD cases, and 0 or 1 in controls.(25) cBraak stage based on amyloid plaques was c in aD cases, and 0 or a in controls.”
BackgroundThe NALP3 inflammasome is involved in the innate immune response to amyloid-β
Halle, A., Hornung, V., Petzold, G. C., Stewart, C. R., Monks, B. G., Reinheckel, T., Fitzgerald, K. A., Latz, E., Moore, K. J., & Golenbock, D. T. (2008) · Nature Immunology · doi:10.1038/ni.1636 · Cited by 2,441
Direct observation of individual endogenous protein complexes in situ by proximity ligation
Söderberg, O., Gullberg, M., Jarvius, M., Ridderstråle, K., Leuchowius, K.-J., Jarvius, J., Wester, K., Hydbring, P., Bahram, F., Larsson, L.-G., et al. (2006) · Nature Methods · doi:10.1038/nmeth947 · Cited by 2,419
Selective autophagy mediated by autophagic adapter proteins
Johansen, T., & Lamark, T. (2011) · Autophagy · doi:10.4161/auto.7.3.14487 · Cited by 1,788
Research works printed but not linked: 1
- Giménez-Xavier P, 2008, Int J Mol Med, 22, 781
Cited by
Sorted by citations
Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?
Leng, F., & Edison, P. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-020-00435-y · Cited by 3,179
Microglia Function in the Central Nervous System During Health and Neurodegeneration
Colonna, M., & Butovsky, O. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052358 · Cited by 2,894
Knopman, D. S., Amieva, H., Petersen, R. C., Chételat, G., Holtzman, D. M., Hyman, B. T., Nixon, R. A., & Jones, D. T. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00269-y · Cited by 2,606
Clearance systems in the brain—implications for Alzheimer disease
Tarasoff-Conway, J. M., Carare, R. O., Osorio, R. S., Glodzik, L., Butler, T., Fieremans, E., Axel, L., Rusinek, H., Nicholson, C., Zlokovic, B. V., et al. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.119 · Cited by 1,678
TREM2 Maintains Microglial Metabolic Fitness in Alzheimer’s Disease
Ulland, T. K., Song, W. M., Huang, S. C.-C., Ulrich, J. D., Sergushichev, A., Beatty, W. L., Loboda, A. A., Zhou, Y., Cairns, N. J., Kambal, A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.023 · Cited by 1,263
Metadata
- 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
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2014-07-22
- Volume
- 10
- Issue
- 10
- Pages
- 1761-1775
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- 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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