Progress in Familial Parkinson's Disease

抄録

We have reviewed recent progress in clinical as well as molecular aspects of familial Parkinson's disease (PD). Three genes have been identified as causes for different forms of familial PD or parkinsonism, i.e., alpha-synuclein, parkin, and tau. In addition, 9 other chromosome loci were identified to be linked to familial PD or dystoniaparkinsonism. Alpha-synuclein mutations cause autosomal dominant levodopa-responsive PD. Parkin mutations cause autosomal recessive young onset familial PD. Tau gene mutations cause familial frontotemporal dementia and parkinsonism linked to chromosome 17. Mutated alpha-synucleins showed an increased tendency for self aggregation into an anti-parallel beta-sheet structure. Parkin protein appears to be essential for the survival of pigmented nuclei of the brain stem. Tau protein is an important microtubule-associated protein. Elucidation of the molecular mechanism of nigral neuronal death due to these mutations will contribute to a better understanding of familial as well as sporadic PD.