Laboratorio de Inmunología Celular y Molecular, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.
Centro de Investigación e Innovación Biomédica (CiiB), Universidad de los Andes, Mons. Álvaro del Portillo 12455, Las Condes, Santiago, Chile.
J Transl Med. 2023 Sep 9;21(1):613. doi: 10.1186/s12967-023-04493-w.
Mitochondrial dysfunction is reiteratively involved in the pathogenesis of diverse neurodegenerative diseases. Current in vitro and in vivo approaches support that mitochondrial dysfunction is branded by several molecular and cellular defects, whose impact at different levels including the calcium and iron homeostasis, energetic balance and/or oxidative stress, makes it difficult to resolve them collectively given their multifactorial nature. Mitochondrial transfer offers an overall solution since it contains the replacement of damage mitochondria by healthy units. Therefore, this review provides an introducing view on the structure and energy-related functions of mitochondria as well as their dynamics. In turn, we summarize current knowledge on how these features are deregulated in different neurodegenerative diseases, including frontotemporal dementia, multiple sclerosis, amyotrophic lateral sclerosis, Friedreich ataxia, Alzheimer´s disease, Parkinson´s disease, and Huntington's disease. Finally, we analyzed current advances in mitochondrial transfer between diverse cell types that actively participate in neurodegenerative processes, and how they might be projected toward developing novel therapeutic strategies.
线粒体功能障碍在多种神经退行性疾病的发病机制中反复出现。目前的体外和体内方法支持线粒体功能障碍的特征是由几种分子和细胞缺陷引起的,其影响在包括钙和铁平衡、能量平衡和/或氧化应激在内的不同水平上,由于其多因素性质,很难将它们集中解决。线粒体转移提供了一个整体解决方案,因为它包含用健康的单位替换受损的线粒体。因此,本综述提供了对线粒体的结构和与能量相关的功能及其动力学的介绍性观点。反过来,我们总结了目前关于这些特征在不同神经退行性疾病中如何失调的知识,包括额颞叶痴呆、多发性硬化症、肌萎缩侧索硬化症、弗里德里希共济失调、阿尔茨海默病、帕金森病和亨廷顿病。最后,我们分析了目前在积极参与神经退行性过程的不同细胞类型之间进行线粒体转移的最新进展,以及它们如何被用于开发新的治疗策略。