Scavenger receptor-mediated adhesion of microglia to beta-amyloid fibrils.
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.
El Khoury
J
J
Department of Physiology, Columbia Univwersity, College of Physicians and Surgeons, New York 10032, USA.
Hickman
S E
SE
Thomas
C A
CA
Cao
L
L
Silverstein
S C
SC
Loike
J D
JD
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins; D051379:Mice; D017628:Microglia / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B
D016229:Amyloid beta-Peptides; D008024:Ligands; D008565:Membrane Proteins; D010455:Peptides; D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051117:Scavenger Receptors, Class A; D051122:Scavenger Receptors, Class B; D003094:Collagen