González Luis F, Bevilacqua Lorenzo E, Naves Rodrigo
Immunology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Av. Independencia 1027, Santiago 8380453, Chile.
Pharmaceutics. 2021 Dec 1;13(12):2055. doi: 10.3390/pharmaceutics13122055.
Mitochondria are vital organelles in eukaryotic cells that control diverse physiological processes related to energy production, calcium homeostasis, the generation of reactive oxygen species, and cell death. Several studies have demonstrated that structural and functional mitochondrial disturbances are involved in the development of different neuroinflammatory (NI) and neurodegenerative (ND) diseases (NI&NDDs) such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Remarkably, counteracting mitochondrial impairment by genetic or pharmacologic treatment ameliorates neurodegeneration and clinical disability in animal models of these diseases. Therefore, the development of nanosystems enabling the sustained and selective delivery of mitochondria-targeted drugs is a novel and effective strategy to tackle NI&NDDs. In this review, we outline the impact of mitochondrial dysfunction associated with unbalanced mitochondrial dynamics, altered mitophagy, oxidative stress, energy deficit, and proteinopathies in NI&NDDs. In addition, we review different strategies for selective mitochondria-specific ligand targeting and discuss novel nanomaterials, nanozymes, and drug-loaded nanosystems developed to repair mitochondrial function and their therapeutic benefits protecting against oxidative stress, restoring cell energy production, preventing cell death, inhibiting protein aggregates, and improving motor and cognitive disability in cellular and animal models of different NI&NDDs.
线粒体是真核细胞中的重要细胞器，控制着与能量产生、钙稳态、活性氧生成和细胞死亡相关的多种生理过程。多项研究表明，线粒体的结构和功能紊乱参与了不同神经炎症（NI）和神经退行性疾病（ND）（NI&NDDs）的发展，如多发性硬化症、阿尔茨海默病、帕金森病、亨廷顿舞蹈症和肌萎缩侧索硬化症。值得注意的是，通过基因或药物治疗对抗线粒体损伤可改善这些疾病动物模型中的神经退行性变和临床残疾。因此，开发能够持续、选择性递送线粒体靶向药物的纳米系统是一种治疗NI&NDDs的新颖且有效的策略。在本综述中，我们概述了与线粒体动力学失衡、线粒体自噬改变、氧化应激、能量缺乏和蛋白病相关的线粒体功能障碍在NI&NDDs中的影响。此外，我们回顾了选择性线粒体特异性配体靶向的不同策略，并讨论了为修复线粒体功能而开发的新型纳米材料、纳米酶和载药纳米系统，以及它们在不同NI&NDDs的细胞和动物模型中对抗氧化应激、恢复细胞能量产生、预防细胞死亡、抑制蛋白质聚集和改善运动及认知残疾方面的治疗益处。
