期刊
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
卷 75, 期 7, 页码 663-672出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/jnen/nlw037
关键词
Cerebellar ataxia; Coenzyme Q10; Multiple system atrophy; Oxidative stress
资金
- National Institutes of Health: NIMH [K01 MH096956]
- National Institutes of Health: NINDS [R01 NS042859, R01 NS39422, R01 NS086736, R01 NS073872, R01 NS085136, R01 NS088257]
- American Brain Foundation Research Training Fellowship
- Parkinson Disease Foundation
- NINDS [K08 NS083738]
- Louis V. Gerstner Jr. Scholarship
- American Parkinson's Disease Association
- International Essential Tremor Foundation
- NIH [P01 HD080642-01]
- Muscle Dystrophy Association (MDA)
- Department of Defense (DOD)
In familial and sporadic multiple system atrophy (MSA) patients, deficiency of coenzyme Q(10) (CoO10) has been associated with mutations in COQ2, which encodes the second enzyme in the CoQ(10) biosynthetic pathway. Cerebellar ataxia is the most common presentation of CoQ(10) deficiency, suggesting that the cerebellum might be selectively vulnerable to low levels of CoQ(10). To investigate whether CoQ(10) deficiency represents a common feature in the brains of MSA patients independent of the presence of COQ2 mutations, we studied CoQ(10) levels in postmortem brains of 12 MSA, 9 Parkinson disease (PD), 9 essential tremor (ET) patients, and 12 controls. We also assessed mitochondrial respiratory chain enzyme activities, oxidative stress, mitochondrial mass, and levels of enzymes involved in CoQ biosynthesis. Our studies revealed CoQ(10) deficiency in MSA cerebellum, which was associated with impaired CoQ biosynthesis and increased oxidative stress in the absence of COQ2 mutations. The levels of CoQ(10) in the cerebella of ET and PD patients were comparable or higher than in controls. These findings suggest that CoQ(10) deficiency may contribute to the pathogenesis of MSA. Because no disease modifying therapies are currently available, increasing CoQ(10) levels by supplementation or upregulation of its biosynthesis may represent a novel treatment strategy for MSA patients.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据