NEUROCHEMICAL AND NEUROGENETIC CORRELATES OF PARKINSONS-DISEASE

We discuss neurochemical and neurogenetic correlates of Parkinson's di sease (PD) based on the recent progress in the study of its etiology a nd pathogenesis. Nigral degeneration with the presence of Lewy bodies in the remaining neurons is the pathologic hallmark of PD, and the res ultant loss of striatal dopamine is responsible for most of the clinic al manifestations. Although the primary cause is still unknown, mitoch ondrial respiratory failure and oxidative stress appear to be two majo r contributors to the nigral cell death. Many endogenous and exogenous compounds with structural similarity to MPTP have been postulated as potential neurotoxins inducing nigral cell death in PD, but there is l ittle evidence of accumulation of such compounds in the nigra. Genetic influence has increasingly been recognized as an important risk facto r for PD. In this respect, genetic linkage analysis and molecular clon ing of the disease genes in familiar parkinsonism are of utmost import ance today. Recently, the disease gene for one of the autosomal domina nt forms of familial PD was identified, and we cloned the gene for an autosomal recessive type of familiar parkinsonism that had been mapped to the long arm of chromosome 6 by our group. Information obtained on farnilial parkinsonism will contribute to the studies on sporadic PD as well.