2. Academic Validation
  3. Hereditary early-onset Parkinson's disease caused by mutations in PINK1

Hereditary early-onset Parkinson's disease caused by mutations in PINK1

  • Science. 2004 May 21;304(5674):1158-60. doi: 10.1126/science.1096284.
Enza Maria Valente 1,  Patrick M Abou-Sleiman,  Viviana Caputo,  Miratul M K Muqit,  Kirsten Harvey,  Suzana Gispert,  Zeeshan Ali,  Domenico Del Turco,  Anna Rita Bentivoglio,  Daniel G Healy,  Alberto Albanese,  Robert Nussbaum,  Rafael González-Maldonado,  Thomas Deller,  Sergio Salvi,  Pietro Cortelli,  William P Gilks,  David S Latchman,  Robert J Harvey,  Bruno Dallapiccola,  Georg Auburger,  Nicholas W Wood
Affiliations

Affiliation

  • 1 CSS IRCCS, Mendel Institute, viale Regina Margherita 261, 00198 Rome, Italy. e.valente@css-mendel.it
PMID: 15087508 DOI: 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.

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