Parkinson disease: etiology, pathogenesis and future of gene therapy

Parkinson disease (PD) is a progressive neurological disorder with a preval ence of 1-2% in people over the age of 50. It has a world-wide distribution and has no gender preference. The neurological hallmark of PD is the prese nce of Lewy bodies and is characterized by the degeneration of nigrostriata l dopaminergic neurons. The causes of PD are unknown but considerable evide nce suggests a multifactorial etiology involving genetic and environmental factors. A molecular genetic approach identified three genes and at least t wo additional loci in rare familial forms of PD. Two of these genes are inv olved in the ubiquitin mediated pathway of protein degradation and the thir d one is a highly expressed protein in the synaptic terminal and is called alpha -synuclein. In animal models, it has been shown that use of the house hold pesticide which is known to contain rotenone, causes PD. Thus, a combi ned action of genetic and environmental factors is responsible for the path ogenesis of PD. Although use of levodopa or dopamine agonists can substanti ally reduce clinical symptoms, and transplantation of fetal nerve tissue st ill remains as an alternative therapy (although it has been recently shown to be having no overall benefit), directed delivery of glial cell derived n eurotrophic factor (known to have trophic effects on dopaminergic neurons) may also be a beneficial therapeutic option for PD patients. (C) 2001 Elsev ier Science Ireland Ltd and the Japan Neuroscience Society. All rights rese rved.