title: Inflammation and the redox-sensitive AGE-RAGE pathway as a therapeutic target in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is the most common cause of dementia. Neuritic amyloid plaques and concomitant chronic inflammation are prominent pathological features of AD. beta-amyloid peptide (Abeta), the major component of plaques, and advanced glycation end products (AGEs), post-translational protein modifications, are key activators of plaque-associated inflammation. Abeta, AGEs, S100b, and amphoterin bind to the receptor for AGEs (RAGE), which transmits the signal from RAGE via redox-sensitive pathways to nuclear factor kappa-B (NF-kappaB)-regulated cytokines. RAGE-mediated inflammation caused by glial cells and subsequent changes in neuronal glucose metabolism are likely to be important contributors to neurodegeneration in AD. As long as the neuronal damage is reversible, drugs interfering with the Abeta and AGE-RAGE pathways might be interesting novel therapeutics for the treatment of AD.
authors.affiliation: Department of Biochemistry and Molecular Biology/Comparative Genomics Centre, James Cook University, Townsville, Australia.
authors.forename: Annette
authors.initials: A
authors.lastname: Maczurek
authors.forename: Kirubakaran
authors.initials: K
authors.lastname: Shanmugam
authors.forename: Gerald
authors.initials: G
authors.lastname: Münch
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*; D003071:Cognition; D005947:Glucose / Q000378:metabolism; D018149:Glucose Intolerance / Q000150:complications; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000150:complications / Q000503:physiopathology*; D010084:Oxidation-Reduction; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology*
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D005947:Glucose