Affiliations: Department of Surgery, Columbia University Medical
Center, NY 10032, USA | Department of Neurology, Columbia University Medical
Center, NY 10032, USA | Department of Pathology, Columbia University Medical
Center, NY 10032, USA | Department of Medicine, Columbia University Medical
Center, NY 10032, USA | School of Dental & Oral Surgery, Columbia
University Medical Center, NY 10032, USA
Note: [] Corresponding author: Dr. Ann Marie Schmidt, Columbia University
Medical Center, 630 West 168 Street, P&S 17-501, NY 10032, USA. Tel.: +1
212 305 6406; Fax: +1 212 305 5337; E-mail: [email protected]
Abstract: The Receptor for Advanced Glycation End Products (RAGE) is a
multiligand member of the immunoglobulin superfamily. RAGE interacts with AGEs,
the products of nonenzymatic glycation/oxidation of proteins and lipids that
accumulate in diverse settings, such as diabetes, inflammation, renal failure,
pro-oxidant states and natural aging. In addition, RAGE is also a receptor for
amyloid-β peptide and β-sheet fibril species. Recent studies
underscore the premise that RAGE interacts with pro-inflammatory molecules,
including S100/calgranulins and amphoterin, the latter also known as high
mobility group box 1 (HMGB1). In chronic neurodegenerative disorders as well as
in nerve tissue upon acute injury, evidence points to upregulation of both RAGE
and these ligand families. In this review, we will discuss the implications of
transient/self-limited upregulation of RAGE and its ligands, vs
sustained/chronic upregulation of this axis in neurodegeneration vs repair in
both the central and peripheral nervous systems. Experimental evidence supports
the premise that RAGE bears both homeostatic and injurious properties in the
nervous system, thereby highlighting "yin/yang" features of this receptor and
its ligand families.
