RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease

SD Yan, XI Chen, J Fu, M Chen, H Zhu, A Roher… - Nature, 1996 - nature.com
SD Yan, XI Chen, J Fu, M Chen, H Zhu, A Roher, T Slattery, L Zhao, M Nagashima, J Morser
Nature, 1996nature.com
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 expression of RAGE in Alzheimer's disease brain …
Abstract
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 expression of RAGE in Alzheimer's disease brain indicates that it is relevant to the pathogenesis of neuronal dysfunction and death.
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