Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
Top Cited Papers
- 21 May 2004
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 304 (5674) , 1158-1160
- https://doi.org/10.1126/science.1096284
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families: a truncating nonsense mutation and a missense mutation at a highly conserved amino acid. Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular stress. These data provide a direct molecular link between mitochondria and the pathogenesis of PD.Keywords
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