UMR CNRS6214, Inserm1083 and department of biochemistry and genetics, CHU d'Angers, 4, rue Larrey, 49933 Angers, France.
UMR CNRS6214, Inserm1083 and department of biochemistry and genetics, CHU d'Angers, 4, rue Larrey, 49933 Angers, France.
Rev Neurol (Paris). 2014 May;170(5):390-400. doi: 10.1016/j.neurol.2014.03.005. Epub 2014 May 1.
Mitochondrial dysfunction has been reported in most neurodegenerative diseases. These anomalies include bioenergetic defect, respiratory chain-induced oxidative stress, defects of mitochondrial dynamics, increase sensitivity to apoptosis, and accumulation of damaged mitochondria with instable mitochondrial DNA. Significant progress has been made in our understanding of the pathophysiology of inherited mitochondrial disorders but most have no effective therapies. The development of new metabolic treatments will be useful not only for rare mitochondrial disorders but also for the wide spectrum of common age-related neurodegenerative diseases shown to be associated with mitochondrial dysfunction. A better understanding of the mitochondrial regulating pathways raised several promising perspectives of neuroprotection. This review focuses on the pharmacological approaches to modulate mitochondrial biogenesis, the removal of damaged mitochondria through mitophagy, scavenging free radicals and also dietary measures such as ketogenic diet.
线粒体功能障碍已在大多数神经退行性疾病中报道。这些异常包括生物能量缺陷、呼吸链诱导的氧化应激、线粒体动力学缺陷、增加对细胞凋亡的敏感性以及不稳定线粒体 DNA 积累的受损线粒体。我们对遗传性线粒体疾病的病理生理学的理解取得了重大进展,但大多数疾病没有有效的治疗方法。新的代谢治疗方法的发展不仅对罕见的线粒体疾病有用,而且对与线粒体功能障碍相关的广泛的常见与年龄相关的神经退行性疾病也有用。对线粒体调节途径的更好理解提出了一些有前途的神经保护观点。这篇综述重点介绍了调节线粒体生物发生、通过自噬清除受损线粒体、清除自由基以及生酮饮食等饮食措施的药理学方法。