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脑疾病中的线粒体移植:成就、方法与挑战

Mitochondrial transplantation in brain disorders: Achievements, methods, and challenges.

作者信息

Riou Aurélien, Broeglin Aline, Grimm Amandine

机构信息

Research Cluster Molecular and Cognitive Neurosciences, Department of Biomedicine, University of Basel, Basel 4055, Switzerland.

Research Cluster Molecular and Cognitive Neurosciences, Department of Biomedicine, University of Basel, Basel 4055, Switzerland; Neurobiology Lab for Brain Aging and Mental Health, University Psychiatric Clinics Basel, Basel 4002, Switzerland.

出版信息

Neurosci Biobehav Rev. 2025 Feb;169:105971. doi: 10.1016/j.neubiorev.2024.105971. Epub 2024 Dec 4.

Abstract

Mitochondrial transplantation is a new treatment strategy aimed at repairing cellular damage by introducing healthy mitochondria into injured cells. The approach shows promise in protecting brain function in various neurological disorders such as traumatic brain injury/ischemia, neurodegenerative diseases, cognitive disorders, and cancer. These conditions are often characterized by mitochondrial dysfunction, leading to impaired energy production and neuronal death. The review highlights promising preclinical studies where mitochondrial transplantation has been shown to restore mitochondrial function, reduce inflammation, and improve cognitive and motor functions in several animal models. It also addresses significant challenges that must be overcome before this therapy can be clinically applied. Current efforts to overcome these challenges, including advancements in isolation techniques, cryopreservation methods, finding an appropriate mitochondria source, and potential delivery routes, are discussed. Considering the rising incidence of neurological disorders and the limited effectiveness of current treatments, this review offers a comprehensive overview of the current state of mitochondrial transplantation research and critically assesses the remaining obstacles. It provides valuable insights that could steer future studies and potentially lead to more effective treatments for various brain disorders.

摘要

线粒体移植是一种新的治疗策略,旨在通过将健康的线粒体引入受损细胞来修复细胞损伤。该方法在保护各种神经疾病(如创伤性脑损伤/缺血、神经退行性疾病、认知障碍和癌症)中的脑功能方面显示出前景。这些病症通常以线粒体功能障碍为特征,导致能量产生受损和神经元死亡。该综述强调了有前景的临床前研究,其中线粒体移植已被证明可在多种动物模型中恢复线粒体功能、减轻炎症并改善认知和运动功能。它还探讨了在该疗法可临床应用之前必须克服的重大挑战。讨论了当前为克服这些挑战所做的努力,包括分离技术、冷冻保存方法、寻找合适的线粒体来源以及潜在的递送途径方面的进展。考虑到神经疾病发病率的上升以及当前治疗效果的有限性,本综述全面概述了线粒体移植研究的现状,并批判性地评估了剩余的障碍。它提供了有价值的见解,可指导未来的研究,并有可能为各种脑部疾病带来更有效的治疗方法。

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