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 52000 Mr. Various deletion mu tations and point mutations have been discovered in patients with autosomal recessive Parkinson's disease. The substantia nigra and the locus coeruleu s selectively undergo neurodegeneration without forming Lewy bodies. The pa rkin 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 te rminus. The function of Parkin was not known until recently. During the yea r 2000, great progress was made in defining its function. First of all, Par kin was found to be a ubiquitin-protein ligase (E3), a component of the ubi quitin system, which is an important adenosine triphosphate-dependent prote in degradation machinery. In addition, CDCrel-1, a synaptic vesicle associa ted 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 rev iew article, we evaluate the developments in this area published since 1 Fe bruary 2000. Curr Opin Neurol 14:477-482. (C) 2001 Lippincott Williams & Wi lkins.