Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson's disease.
Rare monogenic forms of Parkinson's disease (PD) are promoting our understanding of the molecular pathways involved in the common, non-Mendelian forms of the disease. Here, we focus on PARK7, an autosomal recessive form of early-onset parkinsonism caused by mutations in the DJ-1 gene. We first review the genetics of this form and the rapidly expanding knowledge about the structure and biochemical properties of the DJ-1 protein. We also discuss how DJ-1 dysfunction might lead to neurodegeneration, and the implications of this novel piece of information for the pathogenesis of the common PD forms. Although much work remains to be done to clarify the biology of DJ-1, its proposed activity as a molecular chaperone and/or as oxidative sensor appear intriguing in the light of the current theories on the pathogenesis of PD.
Bonifati
Vincenzo
V
Department of Clinical Genetics, Erasmus MC Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands. v.bonifati@erasmusmc.nl
Oostra
Ben A
BA
Heutink
Peter
P
D000293:Adolescent; D000328:Adult; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000502:physiology*; D010300:Parkinson Disease / Q000209:etiology* / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D015398:Signal Transduction
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1