title: AGES in brain ageing: AGE-inhibitors as neuroprotective and anti-dementia drugs?
abstract: In Alzheimer's disease, age-related cellular changes such as compromised energy production and increased radical formation are worsened by the presence of AGEs as additional, AD specific stress factors. Intracellular AGEs (most likely derived from methylglyoxal) crosslink cytoskeletal proteins and render them insoluble. These aggregates inhibit cellular functions including transport processes and contribute to neuronal dysfunction and death. Extracellular AGEs, which accumulate in ageing tissue (but most prominently on long-lived protein deposits like the senile plaques) exert chronic oxidative stress on neurons. In addition, they activate glial cells to produce free radicals (superoxide and NO) and neurotoxic cytokines such as TNF-alpha. Drugs, which inhibit the formation of AGEs by specific chemical mechanisms (AGE-inhibitors), including aminoguanidine, carnosine, tenilsetam, OPB-9195 and pyridoxamine, attenuate the development of (AGE-mediated) diabetic complications. Assuming that 'carbonyl stress' contributes significantly to the progression of Alzheimer's disease, AGE-inhibitors might also become interesting novel therapeutic drugs for treatment of AD.
authors.affiliation: Physiological Chemistry I, Biocenter, University of Würzburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Dukic-Stefanovic
authors.forename: R
authors.initials: R
authors.lastname: Schinzel
authors.forename: P
authors.initials: P
authors.lastname: Riederer
authors.forename: G
authors.initials: G
authors.lastname: Münch
mesh_terms: D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003704:Dementia / Q000188:drug therapy; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D017127:Glycation End Products, Advanced; D018696:Neuroprotective Agents