Evidence of oxidative stress and mitochondrial dysfunction in spinocerebellar ataxia type 2 (SCA2) patient fibroblasts: Effect of coenzyme Q10 supplementation on these parameters

Nanna Cornelius; Jonathan H Wardman; Iain P Hargreaves; Viruna Neergheen; Anne Sigaard Bie; Zeynep Tümer; Jørgen E Nielsen; Troels T Nielsen

doi:10.1016/j.mito.2017.03.001

Evidence of oxidative stress and mitochondrial dysfunction in spinocerebellar ataxia type 2 (SCA2) patient fibroblasts: Effect of coenzyme Q10 supplementation on these parameters

Mitochondrion. 2017 May:34:103-114. doi: 10.1016/j.mito.2017.03.001. Epub 2017 Mar 3.

Authors

Nanna Cornelius¹, Jonathan H Wardman¹, Iain P Hargreaves², Viruna Neergheen³, Anne Sigaard Bie¹, Zeynep Tümer⁴, Jørgen E Nielsen⁵, Troels T Nielsen¹

Affiliations

¹ Neurogenetics Research Laboratory, Danish Dementia Research Centre, Department of Neurology, Rigshospitalet, University of Copenhagen, Denmark.
² Pharmacy and Biomolecular Sciences, James Parsons Building, John Moore's University, Liverpool L3 3AF, United Kingdom.
³ Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, London, United Kingdom.
⁴ Applied Human Molecular Genetics, Kennedy Center, Department of Clinical Genetics, Rigshospitalet, Glostrup, University of Copenhagen, Denmark.
⁵ 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: [email protected].

PMID: 28263872
DOI: 10.1016/j.mito.2017.03.001

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.

Keywords: Mitochondrial function; Neurodegeneration; Oxidative stress; SCA2; Spinocerebellar ataxia type 2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Cells, Cultured
Female
Fibroblasts / pathology*
Humans
Male
Middle Aged
Mitochondria / pathology*
Oxidative Stress*
Spinocerebellar Ataxias / pathology*
Ubiquinone / analogs & derivatives*
Ubiquinone / metabolism
Vitamins / metabolism*
Young Adult

Substances

Vitamins
Ubiquinone
coenzyme Q10