title: Glycation--a sweet tempter for neuronal death.
abstract: Glycation, one of the post-translational modifications of proteins, is a nonenzymatic reaction initiated by the primary addition of a sugar aldehyde or ketone to the amino groups of proteins. In the early stage of glycation, the synthesis of intermediates leading to the formation of Amadori compounds occurs. In the late stage, advanced glycation end products (AGE) are irreversibly formed after a complex cascade of reactions. Several AGEs have been characterized chemically, while other new compounds remain to be identified. To date, studies of the contribution of glycation to diseases have been primarily focused on its relationship to diabetes and diabetes-related complications. However, glucose-induced damage is not limited to diabetic patients. Although it does not cause rapid or remarkable cell damage, glycation advances slowly and accompanies every fundamental process of cellular metabolism. It has recently become clear that glycation also affects physiological aging and neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis. Glycation alters the biological activity of proteins and their degradation processes. Protein cross-linking by AGE results in the formation of detergent-insoluble and protease-resistant aggregates. Such aggregates may interfere with both axonal transport and intracellular protein traffic in neurons. In addition, glycation reactions lead to the production of reactive oxygen species. Conversely, glycation is promoted by oxidative stress. We speculate on the presence of synergism between glycation and oxidative stress. In this review, we provide an outline of glycation and propose some possible mechanisms of its cytotoxicity and defense systems against it.
authors.affiliation: Department of Neurology, Hokkaido University School of Medicine, Kita 15 Nishi 7, Kita-ku, Sapporo, Japan. skikuti@med.hokudai.ac.jp
authors.forename: Seiji
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Shinpo
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Shoichi
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Zenji
authors.initials: Z
authors.lastname: Makita
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sasaki
authors.forename: Kunio
authors.initials: K
authors.lastname: Tashiro
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009420:Nervous System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D009419:Nerve Tissue Proteins; D017382:Reactive Oxygen Species; D005947:Glucose