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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alzheimer Disease / metabolism
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Amino Acid Sequence
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Amyloid beta-Peptides / metabolism*
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Animals
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Cell Adhesion
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Cell Line
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Cell Movement
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Collagen / metabolism
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Humans
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Ligands
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Membrane Proteins*
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Mice
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Microglia / metabolism*
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Microglia / physiology
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Molecular Sequence Data
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Monocytes / physiology
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Peptides / chemical synthesis
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Peptides / metabolism
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Rats
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Reactive Oxygen Species / metabolism
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Receptors, Immunologic / metabolism*
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Receptors, Lipoprotein*
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Receptors, Scavenger
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Scavenger Receptors, Class A
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Scavenger Receptors, Class B
Substances
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Amyloid beta-Peptides
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Ligands
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Membrane Proteins
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Peptides
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Reactive Oxygen Species
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Receptors, Immunologic
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Receptors, Lipoprotein
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Receptors, Scavenger
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Scarb1 protein, mouse
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Scavenger Receptors, Class A
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Scavenger Receptors, Class B
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Collagen