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Cell Mol Life Sci. 2004 Jul;61(14):1729-50.

Unraveling the pathogenesis of Parkinson's disease--the contribution of monogenic forms.

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Department of Clinical Genetics, Room Ee-975, Erasmus MC Rotterdam, P.O. Box 1738, 3000, DR Rotterdam, The Netherlands.


The field of Parkinson's disease pathogenesis is rapidly evolving from the one of a monolithic and obscure entity into the one of a complex scenario with several known molecular players. The ongoing systematic exploration of the genome holds great promise for the identification of the genetic factors conferring susceptibility to the common non-Mendelian forms of this disease. However, most of the progress of the last 5 years has come from the successful mapping and cloning of genes responsible for rare Mendelian variants of Parkinson's disease. These discoveries are providing tremendous help in understanding the molecular mechanisms of this devastating disease. Here we review the genetics of the monogenic forms of Parkinson's disease. Moreover, we focus on the mechanisms of disease caused by alpha-synuclein and parkin mutations, and the implications of this growing body of knowledge for understanding the pathogenesis of the common forms of the disease.

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