title: Parkinsonism due to mutations in PINK1, parkin, and DJ-1 and oxidative stress and mitochondrial pathways.
abstract: Three genes have been identified that cause, in humans, autosomally inherited parkinsonism. These are PARK2, encoding the E3 ubiquitin ligase parkin; PINK1, a mitochondrial kinase; and PARK7, which codes for the protein DJ-1. In several experimental systems, it has been shown that all three proteins impact mitochondrial function and/or oxidative stress responses. These are probably related because mitochondria produce oxidative stress in neurons. Moreover, it is clear that there are relationships between these genes, with a single pathway linking PINK1 and parkin and a parallel relationship with DJ-1. Work in progress in the field is aimed at understanding these relationships in more depth.
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. cookson@mail.nih.gov
authors.forename: Mark R
authors.initials: MR
authors.lastname: Cookson
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000502:physiology; D009154:Mutation / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D018384:Oxidative Stress / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics; D020734:Parkinsonian Disorders / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C105131:PARK7 protein, human