Department of Neurology, College of Medicine, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
Curr Neuropharmacol. 2023;21(5):1100-1116. doi: 10.2174/1570159X05666220908100545.
Neurodegenerative and neurovascular disorders affect millions of people worldwide and account for a large and increasing health burden on the general population. Thus, there is a critical need to identify potential disease-modifying treatments that can prevent or slow the disease progression. Mitochondria are highly dynamic organelles and play an important role in energy metabolism and redox homeostasis, and mitochondrial dysfunction threatens cell homeostasis, perturbs energy production, and ultimately leads to cell death and diseases. Impaired mitochondrial function has been linked to the pathogenesis of several human neurological disorders. Given the significant contribution of mitochondrial dysfunction in neurological disorders, there has been considerable interest in developing therapies that can attenuate mitochondrial abnormalities and proffer neuroprotective effects. Unfortunately, therapies that target specific components of mitochondria or oxidative stress pathways have exhibited limited translatability. To this end, mitochondrial transplantation therapy (MTT) presents a new paradigm of therapeutic intervention, which involves the supplementation of healthy mitochondria to replace the damaged mitochondria for the treatment of neurological disorders. Prior studies demonstrated that the supplementation of healthy donor mitochondria to damaged neurons promotes neuronal viability, activity, and neurite growth and has been shown to provide benefits for neural and extra-neural diseases. In this review, we discuss the significance of mitochondria and summarize an overview of the recent advances and development of MTT in neurodegenerative and neurovascular disorders, particularly Parkinson's disease, Alzheimer's disease, and stroke. The significance of MTT is emerging as they meet a critical need to develop a diseasemodifying intervention for neurodegenerative and neurovascular disorders.
神经退行性和神经血管疾病影响着全球数以百万计的人，并给普通人群带来了巨大且不断增加的健康负担。因此，迫切需要确定潜在的疾病修饰治疗方法，以预防或减缓疾病进展。线粒体是高度动态的细胞器，在能量代谢和氧化还原平衡中发挥重要作用，线粒体功能障碍威胁着细胞内环境的稳定，扰乱能量产生，最终导致细胞死亡和疾病。受损的线粒体功能与几种人类神经疾病的发病机制有关。鉴于线粒体功能障碍在神经疾病中的重要作用，人们对开发能够减轻线粒体异常和提供神经保护作用的治疗方法产生了浓厚的兴趣。不幸的是，针对线粒体特定成分或氧化应激途径的治疗方法的转化能力有限。为此，线粒体移植治疗（MTT）提出了一种新的治疗干预范式，它涉及用健康的线粒体补充受损的线粒体，以治疗神经疾病。先前的研究表明，向受损神经元补充健康供体的线粒体可促进神经元的存活、活性和轴突生长，并已被证明对神经和神经外疾病有益。在这篇综述中，我们讨论了线粒体的重要性，并总结了 MTT 在神经退行性和神经血管疾病（特别是帕金森病、阿尔茨海默病和中风）中的最新进展和发展概况。MTT 的意义正在显现，因为它们满足了为神经退行性和神经血管疾病开发疾病修饰干预措施的迫切需要。
