title: Toxic advanced glycation end products (TAGE) theory in Alzheimer's disease.
abstract: Several epidemiological studies have reported moderately increased risks of Alzheimer's disease (AD) in diabetic patients compared with general population. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress more rapidly. Recent understanding of this process has confirmed that interactions between AGEs and their receptor (RAGE) may play a role in the pathogenesis of diabetic complications and AD. The authors have recently found that glyceraldehyde-derived AGEs (AGE-2), which is predominantly the structure of toxic AGEs (TAGE), show significant toxicity on cortical neuronal cells and that the neurotoxic effect of diabetic serum is completely blocked by neutralizing antibody against the AGE-2 epitope. Moreover, in human AD brains, AGE-2 is distributed in the cytosol of neurons in the hippocampus and parahippocampal gyrus. These results suggest that TAGE is involved in the pathogenesis of AD as well as other age-related diseases. In this review, the authors discuss the molecular mechanisms of AD, especially focusing on TAGE-RAGE system.
authors.affiliation: Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.forename: Noriko
authors.initials: N
authors.lastname: Shimogaito
authors.forename: Xuegang
authors.initials: X
authors.lastname: Wu
authors.forename: Seiji
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic