[Frontiers in Bioscience S4, 240-250, January 1, 2012]

RAGE is a key cellular target for Aβ-induced perturbation in Alzheimer's disease

Shirley ShiDu Yan1,2,3,4, Doris Chen1, Shiqian Yan1, Lan Guo1, Heng Du1, John Xi Chen5

1Department of Surgery, Physicians and Surgeons College of Columbia University, New York, NY 10032, 2Department of Pathology and Cellular biology, Physicians and Surgeons College of Columbia University, New York, NY 10032,3Taub Institute for Research on Alzheimer Disease and the Aging Brain, Physicians and Surgeons College of Columbia University, New York, NY 10032, 4Department of Pharmacology and Toxicology and Higuchi Bioscience Center, University of Kansas4, Lawrence, KS 66047-3729,5Department of Neurology, Memorial Sloan-Kettering Cancer Center4, New York, NY10065

TABLE OF CONTENTS

1. Abstract
2. Introduction
2.1. Structure of RAGE
3. The role of RAGE in the Aβ-induced cellular and molecular events relevant to the pathogenesis of Alzheimer's Disease
3.1. Increased expression of RAGE in AD-affected regions and targeted cells
3.2. RAGE-Aβ interaction mediates neuroinflammation
3.3. RAGE mediates neuronal and synaptic stress
3.4. RAGE and amyloid accumulation in brain
3.5. Other RAGE ligands in Alzheimer's disease
4. Conclusion
5. Acknowledgment
6. References

1. ABSTRACT

RAGE, a receptor for advanced glycation endproducts, is an immunoglobulin-like cell surface receptor that is often described as a pattern recognition receptor due to the structural heterogeneity of its ligand. RAGE is an important cellular cofactor for amyloid β-peptide (Aβ)-mediated cellular perturbation relevant to the pathogenesis of Alzheimer's disease (AD). The interaction of RAGE with Aβ in neurons, microglia, and vascular cells accelerates and amplifies deleterious effects on neuronal and synaptic function. RAGE-dependent signaling contributes to Aβ-mediated amyloid pathology and cognitive dysfunction observed in the AD mouse model. Blockade of RAGE significantly attenuates neuronal and synaptic injury. In this review, we summarize the role of RAGE in the pathogenesis of AD, specifically in Aβ-