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

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 and Wood, Nicholas W (2004) Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science, 304 (5674). pp. 1158-60. ISSN 1095-9203

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Evolution, Behaviour and Environment
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics
Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0447 Genes. Alleles. Genome
Q Science > QH Natural history > QH0301 Biology > QH0426 Genetics > QH0460 Mutations
R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
Depositing User: Dr William Gilks
Date Deposited: 15 Nov 2016 14:59
Last Modified: 15 Nov 2016 14:59
URI: http://sro.sussex.ac.uk/id/eprint/40540
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