Parkin-associated Parkinson's disease.
Mutations in the PARK2 gene coding for parkin cause autosomal recessive juvenile parkinsonism (AR-JP), a familial form of Parkinson's disease (PD). Parkin functions as an E3 ubiquitin ligase, and loss of this ubiquitin ligase activity appears to be the mechanism underlying pathogenesis of AR-JP. Recently, the spectrum of genetic, clinical, and pathological findings on AR-JP has been significantly expanded. Moreover, a considerable number of parkin interactors and/or substrates have been identified and characterized, and animal models of parkin deficiency have been generated. In this review, we provide an overview of the most relevant findings and discuss their implications for the pathogenesis of AR-JP and sporadic PD.
von Coelln
Rainer
R
Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 N. Broadway, Suite 731, Baltimore, MD 21205, USA.
Dawson
Valina L
VL
Dawson
Ted M
TM
D000818:Animals; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism*
D044767:Ubiquitin-Protein Ligases; C111567:parkin protein