title: Targeting the kynurenine pathway as a potential strategy to prevent and treat Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly accounting for the vast majority of dementia. Recently, many studies have implicated the role of inflammatory response, especially neuroinflammatory response in the development and progression of AD. However, the underlying mechanism of how inflammatory response induces AD is unknown. Kynurenine pathway is a major route of the amino acid tryptophan catabolism, resulting in the production of nicotine adenine dinucleotide and other neuroactive intermediates: quinolinic acid (QA) and kynurenic acid (KA). QA exerts different toxic effects, including over-activation of N-methyl-d-aspartate (NMDA) receptor and excitotoxicity, synaptic dysfunction and neuronal death. On the other hand, KA is identified as the only endogenous NMDA receptor antagonist and could modulate neurotoxic effects of QA. We hypothesize that an activated kynurenine pathway induced by inflammatory cytokines would generate more neurotoxic metabolites, which could be closely related to the pathogenesis of AD in elderly patients. Moreover, some measures, which facilitate KA synthesis and reduce the formation of QA, may emerge as a new therapeutic strategy against AD.
authors.affiliation: Department of Urology, The Second Hospital of Chengdu, and Sichuan University, Chengdu, Sichuan 610017, PR China.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Gong
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.forename: Huai-Ming
authors.initials: HM
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Hui-Wei
authors.initials: HW
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000378:metabolism; D007736:Kynurenic Acid / Q000378:metabolism*; D008954:Models, Biological; D017378:Quinolinic Acid / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D017378:Quinolinic Acid; D007736:Kynurenic Acid