Cerebral mitochondrial electron transport chain dysfunction in multiple system atrophy and Parkinson’s disease

To investigate mitochondrial dysfunction in Multiple system atrophy further we examined electron transport chain activity in MSA and control brain tissue, compared with Parkinson’s disease where mitochondrial dysfunction is known to be important

Sandrine C. Foti; Iain Hargreaves; Stephanie Carrington; Aoife P. Kiely; Henry Houlden; Janice L. Holton


Scholarcy highlights

  • Multiple system atrophy is a neurodegenerative disease characterised by glial cytoplasmic inclusions, containing α-synuclein
  • Complex II/III activity was reduced in both brain regions compared with control and this was significant in the cerebellar white matter in MSA cases and in the occipital white matter in Parkinson’s disease
  • In order to address whether the changes observed in electron transport chain activity may be related to changes in protein expression of components of the ETC complexes, immunoblotting was carried on whole homogenate from cerebellar and occipital white matter from control, MSA and PD cases
  • Altered mitochondrial function secondary to alterations in CoQ2 and coenzyme Q10 has been proposed to play a role in the pathogenesis of MSA12,20,21
  • In view of the reduction in CoQ10 levels shown previously, we tested the hypothesis that this would result in disturbed mitochondrial function, manifesting as alterations in the ETC
  • We observed a significant reduction in ETC complex II/III activity in the cerebellar white matter of MSA cases
  • Altered activity of the electron transport chain complexes in the cerebellar white matter with preservation in the occipital lobe strongly supports a role for oligodendroglial mitochondrial dysfunction in the pathogenesis of Multiple system atrophy and the parallels with Parkinson’s disease suggest a common disease mechanism in α-synucleinopathies

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