Parkin and Parkinson's disease

Parkin is the causative gene for an autosomal recessive form of Parkinson's disease. The gene was discovered in 1998. The parkin gene is a novel gene containing 12 exons spanning over 1.5 Mb and encodes a protein of 465 amino acids with a molecular mass of approximately 52,000 M(r). Various deletion mutations and point mutations have been discovered in patients with autosomal recessive Parkinson's disease. The substantia nigra and the locus coeruleus selectively undergo neurodegeneration without forming Lewy bodies. The parkin gene product, Parkin protein, has a unique structure with a ubiquitin-like domain in the amino-terminus and a RING finger motif in the carboxy terminus. The function of Parkin was not known until recently. During the year 2000, great progress was made in defining its function. First of all, Parkin was found to be a ubiquitin-protein ligase (E3), a component of the ubiquitin system, which is an important adenosine triphosphate-dependent protein degradation machinery. In addition, CDCrel-1, a synaptic vesicle associated protein, was found to be a substrate for Parkin as an E3. Although many studies still need to be performed to elucidate the molecular mechanism of the selective nigral neurodegeneration in this form of familial Parkinson's disease, it will not be too long before this is accomplished. In this review article, we evaluate the developments in this area published since 1 February 2000.