title: Neuroprotective function of DJ-1 in Parkinson's disease.
abstract: Parkinson's disease (PD) is caused by dopaminergic neuronal death in the substantia nigra, resulting in a reduced level of dopamine in the striatum. Oxidative stress and mitochondrial dysfunction are thought to be major causes of neurodegeneration in PD. Although genetic and environmental factors are thought to affect the onset of PD, precise mechanisms at the molecular level have not been elucidated. The DJ-1 gene is a causative gene for familial PD (park7) and also an oncogene. DJ-1 has various functions, including transcriptional regulation, antioxidative stress reaction, and chaperone, protease, and mitochondrial regulation, and its activity is regulated by its oxidative status, especially that of cysteine 106 (C106) of DJ-1. Excess oxidation of DJ-1, which renders DJ-1 inactive, has been observed in patients with sporadic PD and Alzheimer's disease, suggesting that DJ-1 also participates in the onset and pathogenesis of sporadic PD as well as familial PD. DJ-1 is also a stress sensor and its expression is increased upon various stresses, including oxidative stress. In this review, we describe functions of DJ-1 against oxidative stress and possible roles of DJ-1 in the pathogenesis of PD.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-ku, Sapporo 060-0812, Japan. hiro@pharm.hokudai.ac.jp
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ariga
authors.forename: Kazuko
authors.initials: K
authors.lastname: Takahashi-Niki
authors.forename: Izumi
authors.initials: I
authors.lastname: Kato
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Niki
authors.forename: Sanae M M
authors.initials: SM
authors.lastname: Iguchi-Ariga
mesh_terms: D000818:Animals; D004298:Dopamine / Q000096:biosynthesis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism*; D015513:Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000235:genetics; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D015513:Oncogene Proteins; D004298:Dopamine