Mendelian forms of Parkinson's disease

Thomas Gasser

Over the last few years, genetic findings have changed our views on Parkinson's disease (PD), as mutations in a growing number of genes are found to cause monogenic forms of the disorder. Point mutations in the gene for α-synuclein, as well as duplications and triplications of the wild-type gene cause a dominant form of PD in rare families, pointing towards mishandling of this protein as a crucial step in the molecular pathogenesis of the disorder. Mutations in the gene for leucine-rich repeat kinase 2 (LRRK2) have recently been identified as a much more common cause for dominant PD, while mutations in the parkin gene, in DJ-1, PINK1 and ATP13A2 all cause autosomal recessive parkinsonism of early onset. Mutations in recessive genes probably are pathogenic through loss-of-function mechanisms, suggesting that their wild-type products protect dopaminergic cells against a variety of insults.

Mots clés: Life Sciences

Thomas Gasser. Mendelian forms of Parkinson's disease. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2009, 1792 (7), pp.587. ⟨10.1016/j.bbadis.2008.12.007⟩. ⟨hal-00492065⟩