Parkinson's--Divergent Causes, Convergent Mechanisms

摘要

Parkinson's disease (PD) is a progressive neurodegenerative illness that affects about 1 million people in North America PD is associated with a profound and selective loss of dopaminergic neurons in the nigrostriatal pathway of the brain, as well asa more widespread (but inadequately characterized) neuronal loss in other brain regions. Clinical manifestations include motor abnormalities (tremor, rigidity, slowness, balance problems), autonom-ic disturbances, psychiatric sequelae (usually depression), and cognitive impairment Although environmental risk factors for PD have received considerable attention, the importance of the genetics underlying susceptibility to PD is increasingly recognized. Despite the overall rarity of the familial forms of PD(<10% of cases), the identification of single genes linked to the disease has yielded crucial insights into possible mechanisms of PD pathogenesis. Now, on page 1158 of this issue, Valente et al. (1) report that a newly identified familial form of PD is caused by a mutation in a putative mitochondrial protein kinase called PINK1 (PTEN-induced kinase 1).