D-β-羟基丁酸可挽救线粒体呼吸并减轻帕金森病的症状。
D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease.
作者信息
Tieu Kim, Perier Celine, Caspersen Casper, Teismann Peter, Wu Du-Chu, Yan Shi-Du, Naini Ali, Vila Miquel, Jackson-Lewis Vernice, Ramasamy Ravichandran, Przedborski Serge
机构信息
Department of Neurology, Columbia University, New York, New York, USA.
出版信息
J Clin Invest. 2003 Sep;112(6):892-901. doi: 10.1172/JCI18797.
Abstract
Parkinson disease (PD) is a neurodegenerative disorder characterized by a loss of the nigrostriatal dopaminergic neurons accompanied by a deficit in mitochondrial respiration. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes dopaminergic neurodegeneration and a mitochondrial deficit reminiscent of PD. Here we show that the infusion of the ketone body d-beta-hydroxybutyrate (DbetaHB) in mice confers partial protection against dopaminergic neurodegeneration and motor deficits induced by MPTP. These effects appear to be mediated by a complex II-dependent mechanism that leads to improved mitochondrial respiration and ATP production. Because of the safety record of ketone bodies in the treatment of epilepsy and their ability to penetrate the blood-brain barrier, DbetaHB may be a novel neuroprotective therapy for PD.
摘要
帕金森病（PD）是一种神经退行性疾病，其特征是黑质纹状体多巴胺能神经元丧失，并伴有线粒体呼吸功能缺陷。1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）是一种神经毒素，可导致多巴胺能神经变性和类似于帕金森病的线粒体缺陷。在此我们表明，向小鼠输注酮体d-β-羟基丁酸酯（DβHB）可部分保护其免受MPTP诱导的多巴胺能神经变性和运动功能缺陷。这些作用似乎是由一种依赖于复合物II的机制介导的，该机制可改善线粒体呼吸和ATP生成。由于酮体在癫痫治疗中的安全记录及其穿透血脑屏障的能力，DβHB可能是一种用于帕金森病的新型神经保护疗法。
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