[Molecular genetics of Parkinson's disease]

Parkinson's disease (PD) is the second most common neurodegenerative disorder in the world. The occurrence of PD is largely sporadic, while several families with Mendelian segregation of PD have been reported. PD is thought to be caused by mitochondrial dysfunction, oxidative stress and inflammation based on multiple genetic and environmental factors, resulting in the apoptosis of dopaminergic cells. Six causal genes for Mendelian inherited PD have been identified to date, which indicate the importance of the ubiquitin-proteasome pathway in the molecular pathogenesis of dopaminergic cell death. Recent studies have also indicated the involvement of genetic factors in the pathogenesis of sporadic PD. Many association studies on candidate genes have examined the relationship between PD and polymorphisms; We identified a-synuclein as a definite susceptibility gene for sporadic PD. Since 2001, significant linkage to several loci have been reported in samples of affected sibling pairs. With the recent advances in human genome analyses, genome-wide association studies by SNP chip are being performed to identify susceptibility genes and to establish tailor-made medicine for PD.