title: Implications for the kynurenine pathway and quinolinic acid in amyotrophic lateral sclerosis.
abstract: The kynurenine pathway (KP) is a major route of L-tryptophan catabolism leading to production of several neurobiologically active molecules. Among them is the excitotoxin quinolinic acid (QUIN) that is known to be involved in the pathogenesis of several major inflammatory neurological diseases. In amyotrophic lateral sclerosis (ALS) degeneration of motor neurons is associated with a chronic and local inflammation (presence of activated microglia and astrocytes). There is emerging evidence that the KP is important in ALS. Recently, we demonstrated that QUIN is significantly increased in serum and CSF of ALS patients. Moreover, most of the factors associated with QUIN toxicity are found in ALS, implying that QUIN may play a substantial role in the neuropathogenesis of ALS. This review details the potential role the KP has in ALS and advances a testable hypothetical model.
authors.affiliation: Centre for Immunology and University of New South Wales, School of Medicine and School of Medical Sciences, Sydney, Australia. g.guillemin@cfi.unsw.edu.au
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
authors.forename: Vincent
authors.initials: V
authors.lastname: Meininger
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Brew
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007737:Kynurenine / Q000378:metabolism*; D008959:Models, Neurological; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D017378:Quinolinic Acid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D007737:Kynurenine; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D017378:Quinolinic Acid