Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Madinah, Saudi Arabia.
Department of Physiology, Neuroscience Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Curr Neuropharmacol. 2023;21(5):1165-1183. doi: 10.2174/1570159X20666220830112408.
Abnormal mitochondrial morphology and metabolic dysfunction have been observed in many neurodegenerative disorders (NDDs). Mitochondrial dysfunction can be caused by aberrant mitochondrial DNA, mutant nuclear proteins that interact with mitochondria directly or indirectly, or for unknown reasons. Since mitochondria play a significant role in neurodegeneration, mitochondriatargeted therapies represent a prosperous direction for the development of novel drug compounds that can be used to treat NDDs. This review gives a brief description of how mitochondrial abnormalities lead to various NDDs such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. We further explore the promising therapeutic effectiveness of mitochondria- directed antioxidants, MitoQ, MitoVitE, MitoPBN, and dimebon. We have also discussed the possibility of mitochondrial gene therapy as a therapeutic option for these NDDs.
在许多神经退行性疾病(NDDs)中都观察到异常的线粒体形态和代谢功能障碍。线粒体功能障碍可能是由异常的线粒体 DNA、直接或间接与线粒体相互作用的突变核蛋白或未知原因引起的。由于线粒体在神经退行性变中起着重要作用,因此靶向线粒体的治疗方法代表了开发新型药物化合物的一个有前途的方向,这些药物化合物可用于治疗 NDDs。本综述简要描述了线粒体异常如何导致各种 NDD,如阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症。我们还进一步探讨了靶向线粒体的抗氧化剂 MitoQ、MitoVitE、MitoPBN 和 dimebon 的有前途的治疗效果。我们还讨论了线粒体基因治疗作为这些 NDD 的治疗选择的可能性。