title: The multiple faces of RAGE--opportunities for therapeutic intervention in aging and chronic disease.
abstract: BACKGROUND
  This review focuses on the multi-ligand receptor of the immunoglobulin superfamily--receptor for advanced glycation endproducts (RAGE). The accumulation of the multiple ligands of RAGE in cellular stress milieux links RAGE to the pathobiology of chronic disease and natural aging.
  
  
  METHODS
  In this review, we present a discussion on the ligands of RAGE and the implications of these ligand families in disease. We review the recent literature on the role of ligand-RAGE interaction in the consequences of natural aging; the macro- and microvascular complications of diabetes; obesity and insulin resistance; autoimmune disorders and chronic inflammation; and tumors and Alzheimer's disease. We discuss the mechanisms of RAGE signaling through its intracellular binding effector molecule--the formin DIAPH1. Physicochemical evidence of how the RAGE cytoplasmic domain binds to the FH1 (formin homology 1) domain of DIAPH1, and the consequences thereof, are also reviewed.
  
  
  CONCLUSIONS
  We discuss the modalities of RAGE antagonism currently in preclinical and clinical studies. Finally, we present the rationale behind potentially targeting the RAGE cytoplasmic domain-DIAPH1 interaction as a logical strategy for therapeutic intervention in the pathological settings of chronic diseases and aging wherein RAGE ligands accumulate and signal.
authors.affiliation: a Diabetes Research Program, Division of Endocrinology, Department of Medicine , New York University Langone Medical Center , New York , NY 10016 , USA.
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Ramasamy
authors.affiliation: b Department of Chemistry , University at Albany, State University of New York , Albany , NY 12222 , USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Shekhtman
authors.affiliation: a Diabetes Research Program, Division of Endocrinology, Department of Medicine , New York University Langone Medical Center , New York , NY 10016 , USA.
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D002908:Chronic Disease; D006801:Humans; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013312:Stress, Physiological / Q000187:drug effects*
chemical_list: D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products
keywords: alzheimer’s disease; diabetes; inflammation; neurodegeneration; obesity; receptor