Sci. Aging Knowl. Environ., 21 April 2004
Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
Enza Maria Valente, 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, and Nicholas W. Woodhttp://sageke.sciencemag.org/cgi/content/abstract/2004/16/or8
Abstract: Science 15 April 2004 (10.1126/science.1096284) (Science Express Reports).
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 which 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.
Science of Aging Knowledge Environment. ISSN 1539-6150