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

E M Valente; P M Abou-Sleiman; V Caputo; M M K Muqit; K Harvey; S Gispert; Z Ali; D Del Turco; A R Bentivoglio; D G Healy; A Albanese; R Nussbaum; R González-Maldonado; T Deller; S Salvi; P Cortelli; W P Gilks; D S Latchman; Robert J Harvey; B Dallapiccola; G Auburger; N W Wood

doi:10.1126/science.1096284

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

Journal article

Peer reviewed

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

E M Valente, P M Abou-Sleiman, V Caputo, M M K Muqit, K Harvey, S Gispert, Z Ali, D Del Turco, A R Bentivoglio, D G Healy, …

Science, Vol.304(5674), pp.1158-1160

2004

DOI: https://doi.org/10.1126/science.1096284

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Abstract

cell culture

chromosomes

genetic engineering

mutagenesis

stresses

mutations

parkinson disease (PD)

diseases

1,2,3,6 tetrahydro 1 methyl 4 phenylpyridine

alpha synuclein

complementary DNA

pesticide

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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Title: Hereditary early-onset Parkinson's disease caused by mutations in PINK1
Authors: E M Valente (Author) - Mendel Institute, Italy
P M Abou-Sleiman (Author) - Institute of Neurology, United Kingdom
V Caputo (Author) - Mendel Institute, Italy
M M K Muqit (Author) - Institute of Neurology, United Kingdom
K Harvey (Author) - University College London, United Kingdom
S Gispert (Author) - J.W. Goethe University, Germany
Z Ali (Author) - J.W. Goethe University, Germany
D Del Turco (Author) - J.W. Goethe University, Germany
A R Bentivoglio (Author) - Catholic University, Italy
D G Healy (Author) - Institute of Neurology, United Kingdom
A Albanese (Author) - National Neurologic Institute Carlo Besta, Italy
R Nussbaum (Author) - National Human Genetics Research Institute, United States
R González-Maldonado (Author) - Hospital Universitatio San Cecilio, Spain
T Deller (Author) - J.W. Goethe University, Germany
S Salvi (Author) - Mendel Institute, Italy
P Cortelli (Author) - University of Modena and Reggio Emilia, italy
W P Gilks (Author) - Institute of Neurology, United Kingdom
D S Latchman (Author) - Institute of Child Health, United Kingdom
Robert J Harvey (Author) - University College London, United Kingdom
B Dallapiccola (Author) - Mendel Institute, Italy
G Auburger (Author) - J.W. Goethe University, Germany
N W Wood (Author) - Institute of Neurology, United Kingdom
Publication details: Science, Vol.304(5674), pp.1158-1160
Publisher: American Association for the Advancement of Science
Date published: 2004
DOI: 10.1126/science.1096284
ISSN: 0036-8075
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English
Record Identifier: 99450318702621
Output Type: Journal article

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Web Of Science research areas: Neurosciences

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