DJ-1, PINK1, and their effects on mitochondrial pathways.
Genetic forms of parkinsonism are interesting for two particular reasons. First, finding a gene identifies a cause for a disease that would otherwise be unexplained. Second, finding several genes for the same disorder allows us to reconstruct molecular pathways that, in the example of Parkinson's disease, are be associated with the survival of dopamine neurons in the substantia nigra. Two rare causes of parkinsonism, DJ-1 and PINK1, are associated with mitochondria. This organelle has long been linked with Parkinson's disease, and recent results are starting to show how mutations impact mitochondrial function. In this short review, I will discuss how we can use some of this information to understand why it is that neurons become dysfunctional in PD.
Cookson
Mark R
MR
Cell Biology and Gene Expression Unit, Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, Maryland 20982-3707, USA. cookson@mail.nih.gov
D000818:Animals; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D020734:Parkinsonian Disorders / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase; C105131:PARK7 protein, human