title: Indoleamine 2,3 Dioxygenase as a Potential Therapeutic Target in Huntington's Disease.
abstract: Within the past decade, there has been increasing interest in the role of tryptophan (Trp) metabolites and the kynurenine pathway (KP) in diseases of the brain such as Huntington's disease (HD). Evidence is accumulating to suggest that this pathway is imbalanced in neurologic disease states. The KP diverges into two branches that can lead to production of either neuroprotective or neurotoxic metabolites. In one branch, kynurenine (Kyn) produced as a result of tryptophan (Trp) catabolism is further metabolized to neurotoxic metabolites such as 3-hydroxykunurenine (3-HK) and quinolinic acid (QA). In the other branch, Kyn is converted to the neuroprotective metabolite kynurenic acid (KA). The enzyme Indoleamine 2,3 dioxygenase (IDO1) catalyzes the conversion of Trp into Kyn, the first and rate-limiting enzymatic step of the KP. This reaction takes place throughout the body in multiple cell types as a required step in the degradation of the essential amino acid Trp. Studies of IDO1 in brain have focused primarily on a potential role in depression, immune tolerance associated with brain tumours, and multiple sclerosis; however the role of this enzyme in neurodegenerative disease has garnered significant attention in recent years. This review will provide a summary of the current understanding of the role of IDO1 in Huntington's disease and will assess this enzyme as a potential therapeutic target for HD.
authors.affiliation: Centre for Molecular Medicine & Therapeutics and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Gelareh
authors.initials: G
authors.lastname: Mazarei
authors.affiliation: Centre for Molecular Medicine & Therapeutics and Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Blair R
authors.initials: BR
authors.lastname: Leavitt
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology; D000818:Animals; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy / Q000201:enzymology* / Q000517:prevention & control*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors*; D007737:Kynurenine / Q000378:metabolism*; D010300:Parkinson Disease / Q000201:enzymology; D015398:Signal Transduction; D014364:Tryptophan / Q000378:metabolism
chemical_list: C576710:IDO1 protein, human; C576711:IDO2 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan
keywords: Huntington’s disease; huntingtin; indoleamine 2,3 dioxygenase; kynurenine pathway; quinolinic acid; tryptophan