Scavenger receptor-mediated adhesion of microglia to β-amyloid fibrils
Abstract
A pathological hallmark of Alzheimer's disease is the senile plaque, containing beta-amyloid fibrils, microglia and astrocytes. Beta-amyloid fibrils exert a cytotoxic effect on neurons, and stimulate microglia to produce neurotoxins, such as reactive oxygen species. Mononuclear phagocytes, including microglia, express scavenger receptors that mediate endocytosis of oxidized low-density lipoproteins, and adhesion to glucose-modified extra-cellular matrix proteins. Here we report that class A scavenger receptors mediate adhesion of rodent microglia and human monocytes to beta-amyloid fibril-coated surfaces leading to secretion of reactive oxygen species and cell immobilization. Thus, class A scavenger receptors are potential therapeutic targets in Alzheimer's disease.
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Aβ clearance involves microglial phagocytosis and endocytosis via scavenger receptors and extracellular degradation by Aβ-degrading enzymes.
“Aβ clearance involves, in part36, phagocytosis and endocytosis via microglial scavenger receptors (SRs)37,38 and extracellular degradation by Aβ-degrading enzymes6,36.”
From Microglia in neurodegeneration (2018) · cites this paper as [38]
Microglia around Aβ plaques in humans and Aβ-mice express SR-A1, a receptor that phagocytoses Aβ.
“SR-A1 is an Aβ-phagocytic receptor37,38 expressed on microglia surrounding Aβ plaques in humans and Aβ-mice.”
From Microglia in neurodegeneration (2018) · cites this paper as [38]
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- Authors
- Khoury, J. E., Hickman, S. E., Thomas, C. A., Cao, L., Silverstein, S. C., & Loike, J. D.
- Affiliations
- Columbia University (US)
- Venue
- Nature
- Published
- 1996-08
- Volume
- 382
- Issue
- 6593
- Pages
- 716-719
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2045560271
- Cited by
- 727
- References
- 21
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 12 · 2023: 10 · 2022: 18 · 2021: 19 · 2020: 20 · 2019: 15 · 2018: 12 · 2017: 10 · 2016: 18 · 2015: 21 · 2014: 20 · 2013: 22 · 2012: 31
- FWCI
- 29.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- scavenger receptors, scavenger receptor A, microglia, amyloid-beta fibrils, Alzheimer's disease, amyloid plaques, reactive oxygen species, monocytes, cell immobilization, therapeutic target
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Animals, Cell Adhesion, Cell Line, Cell Movement, Collagen, Humans, Ligands, Membrane Proteins, Molecular Sequence Data, Monocytes, Peptides, Receptors, Immunologic, Amyloid beta-Peptides, Reactive Oxygen Species, Microglia, Receptors, Lipoprotein, Receptors, Scavenger, Scavenger Receptors, Class A, Scavenger Receptors, Class B, Mice, Rats
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