RAGE: a journey from the complications of diabetes to disorders of the nervous system - striking a fine balance between injury and repair.
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-beta peptide and beta-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.
Department of Surgery, Columbia University Medical Center, NY 10032, USA.
Ling Ling
LL
Rong
Clifton
C
Gooch
Mattias
M
Szabolcs
Kevan C
KC
Herold
Evanthia
E
Lalla
Arthur P
AP
Hays
Shi Fang
SF
Yan
Shirley Shi Du
SS
Yan
Ann Marie
AM
Schmidt
D000818:Animals; D048909:Diabetes Complications / Q000150:complications* / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism; D013312:Stress, Physiological / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D039841:Leukocyte L1 Antigen Complex; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins