title: Evidence of oxidative stress and mitochondrial dysfunction in spinocerebellar ataxia type 2 (SCA2) patient fibroblasts: Effect of coenzyme Q10 supplementation on these parameters.
abstract: Spinocerebellar ataxia type 2 (SCA2) is a rare neurodegenerative disorder caused by a CAG repeat expansion in the ataxin-2 gene. We show increased oxidative stress, abnormalities in the antioxidant system, changes in complexes involved in oxidative phosphorylation and changes in mitochondrial morphology in SCA2 patient fibroblasts compared to controls, and we show that treatment with CoQ10 can partially reverse these changes. Together, our results suggest that oxidative stress and mitochondrial dysfunction may be contributory factors to the pathophysiology of SCA2 and that therapeutic strategies involving manipulation of the antioxidant system could prove to be of clinical benefit.
authors.affiliation: Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Nanna
authors.initials: N
authors.lastname: Cornelius
authors.affiliation: Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Wardman
authors.affiliation: Pharmacy and Biomolecular Sciences, James Parsons Building, John Moore's University, Liverpool L3 3AF, United Kingdom.
authors.forename: Iain P
authors.initials: IP
authors.lastname: Hargreaves
authors.affiliation: Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.
authors.forename: Viruna
authors.initials: V
authors.lastname: Neergheen
authors.affiliation: Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Anne Sigaard
authors.initials: AS
authors.lastname: Bie
authors.affiliation: Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Rigshospitalet, Glostrup, University of Copenhagen, Denmark.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Tümer
authors.affiliation: Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark; Danish Dementia Research Centre, Neurogenetics Clinic, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark; Section of Neurogenetics, Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Denmark. Electronic address: joergen.erik.nielsen.01@regionh.dk.
authors.forename: Jørgen E
authors.initials: JE
authors.lastname: Nielsen
authors.affiliation: Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
authors.forename: Troels T
authors.initials: TT
authors.lastname: Nielsen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology*; D018384:Oxidative Stress; D020754:Spinocerebellar Ataxias / Q000473:pathology*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism; D014815:Vitamins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014815:Vitamins; D014451:Ubiquinone; C024989:coenzyme Q10
keywords: Mitochondrial function; Neurodegeneration; Oxidative stress; SCA2; Spinocerebellar ataxia type 2