Reductions in COQ2 Expression Relate to Reduced ATP Levels in Multiple System Atrophy Brain

Jen-Hsiang T Hsiao; Sivaraman Purushothuman; Poul H Jensen; Glenda M Halliday; Woojin Scott Kim

doi:10.3389/fnins.2019.01187

Reductions in COQ2 Expression Relate to Reduced ATP Levels in Multiple System Atrophy Brain

Front Neurosci. 2019 Nov 1:13:1187. doi: 10.3389/fnins.2019.01187. eCollection 2019.

Authors

Jen-Hsiang T Hsiao^{1

2}, Sivaraman Purushothuman¹, Poul H Jensen³, Glenda M Halliday^{1

2}, Woojin Scott Kim^{1

2}

Affiliations

¹ Brain and Mind Centre and Central Clinical School, The University of Sydney, Sydney, NSW, Australia.
² School of Medical Sciences, University of New South Wales & Neuroscience Research Australia, Randwick, NSW, Australia.
³ Department of Biomedicine, DANDRITE-Danish Research Institute of Translational Neuroscience, Aarhus University, Aarhus, Denmark.

Abstract

Multiple system atrophy (MSA) is a progressive neurodegenerative disease clinically characterized by parkinsonism and cerebellar ataxia, and pathologically by oligodendrocyte α-synuclein inclusions. Genetic variants of COQ2 are associated with an increased risk for MSA in certain populations. Also, deficits in the level of coenzyme Q₁₀ and its biosynthetic enzymes are associated with MSA. Here, we measured ATP levels and expression of biosynthetic enzymes for coenzyme Q₁₀, including COQ2, in multiple regions of MSA and control brains. We found a reduction in ATP levels in disease-affected regions of MSA brain that associated with reduced expression of COQ2 and COQ7, supporting the concept that abnormalities in the biosynthesis of coenzyme Q₁₀ play an important role in the pathogenesis of MSA.

Keywords: ATP; COQ2; COQ7; cerebellum; coenzyme Q10; multiple system atrophy; parkinsonian disorders.

Grants and funding

R28 AA012725/AA/NIAAA NIH HHS/United States