The role of RAGE in amyloid-beta peptide-mediated pathology in Alzheimer's disease

Curr Opin Investig Drugs. 2009 Jul;10(7):672-80.

Abstract

This review discusses current knowledge of the complex interactions between amyloid-beta (A beta) peptide, the receptor for advanced glycation endproducts (RAGE), and inflammatory mediators, focusing on the roles of such interactions in the pathogenesis of Alzheimer's disease. As a ubiquitous cell-surface receptor, RAGE demonstrates enhanced expression in an A beta-rich environment; the effects of RAGE on microglia, the blood-brain barrier and neurons are mediated through various signaling pathways. Relevant preclinical models illustrate that the A beta-RAGE interaction amplifies neuronal stress and the accumulation of A beta, impairs memory and learning, and exaggerates neuroinflammation. These findings suggest that RAGE may mediate a common proinflammatory pathway in neurodegenerative disorders.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / pharmacology
  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Disease Models, Animal
  • Humans
  • Inflammation / etiology*
  • Mice
  • Models, Biological
  • Neurodegenerative Diseases / metabolism
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / agonists
  • Receptors, Immunologic / physiology*

Substances

  • Amyloid beta-Peptides
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic