What does PINK1 mean for Parkinson diseases?

Abstract

Disease is very old, and nothing about it has changed. It is we who change, as we learn to recognize what was formerly imperceptible. — —Jean-Martin Charcot The suggestion of a genetic influence within Parkinson disease (PD) dates back to 1880 when Charcot’s student Leroux proclaimed, “A true cause of paralysis agitans, and perhaps the only true one, is heredity.” A brief search of McKusik’s Online Mendelian Inheritance in Man at www.ncbi.nlm.nih.gov/ entrez/query.fcgi?db=OMIM (OMIM database) reveals this to be prescient. There are now 10 PARK loci, each representing a genomic region linked with varying degrees of evidence, to PD-like disorders. Four PARK loci have been definitively shown to contain gene mutations associated with parkinsonism ( PARK-1 , -2 , -6 and -7 ). The identification of mutations within the α-synuclein gene ( PARK-1 )1 was proof of principle for genetic research in PD and the discovery that α-synuclein is an abundant component of the pathological hallmark inclusion of PD, the Lewy body,2 demonstrated that genetics of rare familial forms of parkinsonism bears relevance to typical PD. The subsequent discovery of mutations in parkin ( PARK-2 ) and DJ-1 ( PARK-7 ) increased the repertory of tools researchers have at hand to dissect out disease pathways.3,4⇓ For many laboratories the holy grail of this research is to link these proteins together in a single molecular pathway, the identification of which …