Genetics of Parkinson's disease

The etiology of most cases of Parkinson's disease (PD) remains unknown. In recent years, however, research has successfully focused on genetic factors contributing to the degeneration of dopaminergic neurons. Causative mutations have been identified in several monogenically inherited forms of the disease. Although these genetic forms of PD are usually rare, the gene discoveries are likely to identify molecular pathways that are also relevant in the sporadic disorder. These studies have led to the identification of (i) the central role of α-synuclein aggregation, secondary to either point mutations or an amplification of the α-synuclein gene; and (ii) the relevance of defects in the proteasomal protein degradation pathway in the molecular pathogenesis of recessive parkin-linked forms of PD. The recent discoveries of two additional recessive forms associated with mutations in the genes DJ-1 and PINK1 have brought the mitochondrial energy metabolism and the cell's defence against toxic free radicals into the focus of research.