RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease.
Amyloid-beta peptide is central to the pathology of Alzheimer's disease, because it is neurotoxic--directly by inducing oxidant stress, and indirectly by activating microglia. A specific cell-surface acceptor site that could focus its effects on target cells has been postulated but not identified. Here we present evidence that the 'receptor for advanced glycation end products' (RAGE) is such a receptor, and that it mediates effects of the peptide on neurons and microglia. Increased expressing of RAGE in Alzheimer's disease brain indicates that it is relevant to the pathogenesis of neuronal dysfunction and death.
Yan
S D
SD
Department of Pathology, Columbia University, College of Physicians and Surgeons, New York 10032, USA.
Chen
X
X
Fu
J
J
Chen
M
M
Zhu
H
H
Roher
A
A
Slattery
T
T
Zhao
L
L
Nagashima
M
M
Morser
J
J
Migheli
A
A
Nawroth
P
P
Stern
D
D
Schmidt
A M
AM
D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D051379:Mice; D017628:Microglia / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D016716:PC12 Cells; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000302:isolation & purification / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D017931:DNA Primers; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic