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Hereditary early-onset Parkinson's disease caused by mutations in PINK1 |
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| 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 |
| Institution: | CSS IRCCS, Mendel Institute, viale Regina Margherita 261, 00198 Rome, Italy. e.valente@css-mendel.it |
| 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. |
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