ABSTRACT
Mutations in the parkin gene (PRKN) have been recognized as a major cause of earlyonset parkinsonism with recessive inheritance. Up to 50% of familial and 15 to 20% of sporadic young-onset cases may be due to PRKN mutations. Although the neuropathologic changes found in parkin-related parkinsonism differ from those of typical idiopathic Parkinson’s disease (PD) because of the absence of the characteristic alpha-synuclein positive inclusions (Lewy-bodies and Lewy-neurites), the understanding of the underlying molecular events is thought to provide important insight into the mechanisms of selective neuronal cell death. The study of the normal function of parkin and its dysfunction in several cellular and animal models showed that defective protein degradation by the ubiquitin-proteasome complex and/or early mitochondrial dysfunction and increased oxidative cell damage may be central to the pathogenic cascade.
