Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

Autor:	Sepe S; Department of Molecular Genetics, Erasmus Medical Center, 3015 Rotterdam, the Netherlands., Milanese C; Department of Molecular Genetics, Erasmus Medical Center, 3015 Rotterdam, the Netherlands; Ri.Med Foundation, 90133 Palermo, Italy., Gabriels S; Department of Molecular Genetics, Erasmus Medical Center, 3015 Rotterdam, the Netherlands., Derks KW; Department of Molecular Genetics, Erasmus Medical Center, 3015 Rotterdam, the Netherlands., Payan-Gomez C; Department of Molecular Genetics, Erasmus Medical Center, 3015 Rotterdam, the Netherlands; Facultad de Ciencias Naturales y Matemáticas, Universidad del Rosario, 111711 Bogotá, Colombia., van IJcken WF; Center for Biomics, Erasmus Medical Centre, 3015 Rotterdam, the Netherlands., Rijksen YM; Department of Molecular Genetics, Erasmus Medical Center, 3015 Rotterdam, the Netherlands., Nigg AL; Optical Imaging Center, Erasmus Medical Centre, 3015 Rotterdam, the Netherlands., Moreno S; University of 'Roma Tre,' 00146 Rome, Italy., Cerri S; Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, C. Mondino National Neurological Institute, 27100 Pavia, Italy., Blandini F; Laboratory of Functional Neurochemistry, Center for Research in Neurodegenerative Diseases, C. Mondino National Neurological Institute, 27100 Pavia, Italy., Hoeijmakers JH; Department of Molecular Genetics, Erasmus Medical Center, 3015 Rotterdam, the Netherlands., Mastroberardino PG; Department of Molecular Genetics, Erasmus Medical Center, 3015 Rotterdam, the Netherlands. Electronic address: p.g.mastroberardino@erasmusmc.nl.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2016 May 31; Vol. 15 (9), pp. 1866-75. Date of Electronic Publication: 2016 May 19.
DOI:	10.1016/j.celrep.2016.04.071
Abstrakt:	The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD. (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu