title: TRYCAT pathways link peripheral inflammation, nicotine, somatization and depression in the etiology and course of Parkinson's disease.
abstract: Increased depression, somatization, gut inflammation and wider peripheral inflammation are all associated with the early stages of Parkinson's disease (PD). Classically such concurrent conditions have been viewed as "comorbidities", driven by high levels of stress in a still poorly understood and treated disorder. Here we review the data on how oxidative and nitrosative stress in association with immuno-inflammatory responses, drives alteration in tryptophan catabolites, including kynurenine, kynurenic acid and quinolinic acid that drive not only the 'comorbidities" of PD but also important processes in the etiology and course of PD per se. The induction of indoleamine 2,3-dioxygenase, leading to the driving of tryptophan into neuroregulatory tryptophan catabolite products and away from serotonin and melatonin production, has significant implications for understanding the role of nicotine, melatonin, and caffeine in regulating PD susceptibility. Tryptophan catabolite pathway activation will also regulate blood-brain barrier permeability, glia and mast cell reactivity as well as wider innate and adaptive immune cell responses, all relevant to the course of PD. As such, the "comorbidities" of PD such as depression, somatization and peripheral inflammatory disorders can all be conceptualized as being an intricate part of the biological underpinnings of both the etiology and course of PD. As a consequence, the data reviewed here has treatment implications; relevant to both the course of PD and in the management of L-DOPA induced dyskinesias.
authors.forename: George
authors.initials: G
authors.lastname: Anderson
authors.affiliation: George Anderson, CRC, Rm 30, 57 Laurel St. Glasgow G11 7QT, Scotland. anderson.george@rocketmail.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Maes
mesh_terms: D000818:Animals; D003863:Depression / Q000209:etiology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007249:Inflammation / Q000209:etiology*; D009538:Nicotine / Q000378:metabolism*; D010300:Parkinson Disease / Q000150:complications* / Q000628:therapy; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013001:Somatoform Disorders / Q000209:etiology*; D014364:Tryptophan / Q000378:metabolism*
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D009538:Nicotine; D014364:Tryptophan