Plasma Coenzyme Q10 Levels in Patients With Multiple System Atrophy

Mitsui, Jun; Matsukawa, Takashi; Yasuda, Tsutomu; Ishiura, Hiroyuki; Tsuji, Shoji

doi:10.1001/jamaneurol.2016.1325

Cited by 45 publications

(38 citation statements)

References 17 publications

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“…However, based on pathological and molecular evidence from MSA human studies and animal models, several factors seem to be definitely associated with the disease and may serve as therapeutic targets for disease modification (Fig. 1), including the abnormal accumulation of α-syn [30][31][32][33]43,44], microglial activation and neuroinflammation [52,[54][55][56][57][58][59][60][61]89], autophagy disturbances [64][65][66][67], mitochondrial dysfunction [12,15,66,[68][69][70][71][72][73][74] and oxidative stress [76]. Yet the primary event which triggers the whole pathogenic cascade is still unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, MSA patients showed reduced levels of CoQ10 in cerebrospinal fluid, plasma/serum and cerebellum [68][69][70][71][72][73], which may lead to decreased electron transport in mitochondria and increased vulnerability to oxidative stress [68,69]. Recent studies with MSA fibroblast and iPSCs-derived dopaminergic neurons observed reduced CoQ10 levels and up-regulation of some CoQ10 biosynthesis enzymes in MSA patients compared to healthy controls [66,67,74].…”

Section: Other Translational Therapies For Msamentioning

confidence: 99%

“…It is thought that the neurodegenerative process underlying MSA results from the interaction of multiple factors, including the abnormal accumulation of α-syn, microglial activation and neuroinflammation, genetic polymorphisms, dysregulation of myelin lipids [62,63], disturbances of autophagy [64][65][66][67], mitochondrial [12,15,66,[68][69][70][71][72][73][74] and proteasomal dysfunction [75,76] and oxidative stress [74,76]. At present there is no cure for MSA and only mitigation of some symptoms is feasible.…”

Section: Introductionmentioning

confidence: 99%

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MSA: From basic mechanisms to experimental therapeutics

Heras‐Garvin

Stefanova

2020

Parkinsonism & Related Disorders

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Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder characterized by rapidly progressive autonomic and motor dysfunction. Pathologically, MSA is mainly characterized by the abnormal accumulation of misfolded α-synuclein in the cytoplasm of oligodendrocytes, which plays a major role in the pathogenesis of the disease. Striatonigral degeneration and olivopontecerebellar atrophy underlie the motor syndrome, while degeneration of autonomic centers defines the autonomic failure in MSA. At present, there is no treatment that can halt or reverse its progression. However, over the last decade several studies in preclinical models and patients have helped to better understand the pathophysiological events underlying MSA. The etiology of this fatal disorder remains unclear and may be multifactorial, caused by a combination of factors which may serve as targets for novel therapeutic approaches. In this review, we summarize the current knowledge about the etiopathogenesis and neuropathology of MSA, its different preclinical models, and the main disease modifying therapies that have been used so far or that are planned for future clinical trials.

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Section: Discussionmentioning

confidence: 99%

Section: Other Translational Therapies For Msamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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MSA: From basic mechanisms to experimental therapeutics

Heras‐Garvin

Stefanova

2020

Parkinsonism & Related Disorders

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“…After controlling for COQ2 genotypes, patients with MSA still had significantly lower levels of CoQ10, indicating that the lower plasma levels of CoQ10 in patients with MSA cannot be attributed to COQ2 mutations. 12 In addition, patients with the cerebellar and parkinsonism subtypes of MSA had similarly decreased plasma levels of CoQ10. Consistent with these observations, Kasai et al 13 found a decreased ratio of serum CoQ10 to cholesterol in patients with MSA.…”

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confidence: 99%

“…And, if so, might it serve as a biomarker for MSA? In this issue of JAMA Neurology , Mitsui and colleagues 12 have addressed these issues by investigating plasma levels of CoQ10 in 44 patients with MSA and 39 controls. They found a 30% reduction of plasma levels of CoQ10 in patients with MSA.…”

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confidence: 99%

Coenzyme Q10 as a Peripheral Biomarker for Multiple System Atrophy

Kuo

Quinzii

2016

JAMA Neurol

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Plasma Coenzyme Q10 Levels and Multiple System Atrophy

2016

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To the Editor We read with interest the study by Mitsui and colleagues 1 who found decreased levels of plasma coenzyme Q10 (CoQ10) in patients with multiple system atrophy (MSA) regardless of the COQ2 genotype. Mutations in CoQ2 (which encodes an essential enzyme in the biosynthetic pathway of CoQ10) have previously been shown to be associated with MSA. 2 Mitsui et al 1 found a lower plasma CoQ10 level in those with MSA compared with controls (95% CI, 0.10; range, 0.02-0.66) (P = .02). Owing to the small sample size, the reference level of plasma CoQ2 used in the comparison had a major influence in the conclusion.The mean (SD) plasma CoQ10 level reported in the study was 0.51 (0.22) vs 0.72 (0.42) μg/mL in patients with MSA and healthy controls, respectively. While the authors highlighted that this was comparable with the mean (SD) serum CoQ10 level of 985.3 (939.4) nmol/L (equal to 0.85 [0.81] μg/mL; n = 18) by Kasai et al 3 and mean (SD) plasma CoQ10 level of 757 (247) nM (equal to 0.65 [0.21] μg/mL; n = 20) by Sohmiya et al 4 in healthy Japanese controls, the sample sizes of all these studies were rather small. We would like to draw the authors' attention to a recent study by Iwasaki and colleagues 5 who reported the median plasma CoQ10 in healthy Japanese individuals from Tokyo to be 1.02 μg/mL (range, 0.93-1.11 μg/mL). This level gathered from a much larger sample size (n = 141) 5 was much higher than the level in the controls in the study by Mitsui et al. 1 This suggests that the plasma CoQ2 level in healthy controls may be 2 times higher than in patients with MSA in the Japanese population. The magnitude of this difference certainly elevates the clinical relevance and significance of the conclusions by Mitsui et al. 1 The authors have prudently excluded potential confounding variables (such as dyslipidemia and some drugs that potentially interact with CoQ10) in their study participants. Cholesterol influences CoQ10 levels by creating a conjugated form in blood, 3 but this is not an "all or nothing" interaction. Hence, we think that measurements of the cholesterol levels in both patients with MSA and healthy controls should have been taken into account in the analysis using a multivariate regression model.If CoQ10 levels are indeed consistently low in patients with MSA, the more challenging question is whether CoQ10 supplementation in patients with MSA with low CoQ2 level will be able to improve clinical symptoms or retard disease progression. We await with great interest for future studies to address this.

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Plasma Coenzyme Q10 Levels in Patients With Multiple System Atrophy

Cited by 45 publications

References 17 publications

MSA: From basic mechanisms to experimental therapeutics

MSA: From basic mechanisms to experimental therapeutics

Coenzyme Q10 as a Peripheral Biomarker for Multiple System Atrophy

Plasma Coenzyme Q10 Levels and Multiple System Atrophy

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