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- Title
Hereditary early-onset Parkinson's disease caused by mutations in PINK1.
- Authors
Valente, Enza Maria; Abou-Sleiman, Patrick M; Caputo, Viviana; Muqit, Miratul M K; Harvey, Kirsten; Gispert, Suzana; Ali, Zeeshan; Del Turco, Domenico; Bentivoglio, Anna Rita; Healy, Daniel G; Albanese, Alberto; Nussbaum, Robert; González-Maldonado, Rafael; Deller, Thomas; Salvi, Sergio; Cortelli, Pietro; Gilks, William P; Latchman, David S; Harvey, Robert J; Dallapiccola, Bruno; Auburger, Georg; Wood, Nicholas W
- 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.
- Publication
Science (New York, N.Y.), 2004, Vol 304, Issue 5674, p1158
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1096284