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正常及病理性衰老过程中脑细胞的线粒体动力学

Mitochondrial Dynamics in Brain Cells During Normal and Pathological Aging.

作者信息

Sukhorukov Vladimir S, Baranich Tatiana I, Egorova Anna V, Akateva Anastasia V, Okulova Kseniia M, Ryabova Maria S, Skvortsova Krisitina A, Dmitriev Oscar V, Mudzhiri Natalia M, Voronkov Dmitry N, Illarioshkin Sergey N

机构信息

Laboratory of Neuromorphology, Brain Science Institute, Research Center of Neurology, Moscow 125367, Russia.

出版信息

Int J Mol Sci. 2024 Nov 29;25(23):12855. doi: 10.3390/ijms252312855.

Abstract

Mitochondrial dynamics significantly play a major role in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. The dysregulation of mitochondrial biogenesis and function, characterized by impaired fission and fusion processes mediated by a number of proteins, in particular, Drp1, Mfn1, Mfn2, Opa1, and PGC-1α, contributes to neuronal vulnerability and degeneration. Insufficient mitophagy and disrupted mitochondrial transport exacerbate oxidative stress and neurotoxicity. Emerging therapeutic strategies that target mitochondrial dynamics, including various pharmacological agents, demonstrate potential for restoring mitochondrial balance and enhancing neuroprotection. This growing body of research underscores the importance of mitochondrial health in developing effective interventions for neurodegenerative conditions. This review highlights well-established links between the disruption of mitochondrial dynamics and the development of neurodegenerative processes. We also discuss different therapeutic strategies that target mitochondrial function in neurons that have been proposed as perspective neuroprotective treatments.

摘要

线粒体动力学在神经退行性疾病(如帕金森病和阿尔茨海默病)的发病机制中起着重要作用。线粒体生物发生和功能的失调,其特征是由多种蛋白质(特别是Drp1、Mfn1、Mfn2、Opa1和PGC-1α)介导的裂变和融合过程受损,导致神经元易损性和变性。线粒体自噬不足和线粒体运输中断会加剧氧化应激和神经毒性。针对线粒体动力学的新兴治疗策略,包括各种药物制剂,显示出恢复线粒体平衡和增强神经保护的潜力。这一不断增长的研究领域强调了线粒体健康在制定有效的神经退行性疾病干预措施中的重要性。本综述强调了线粒体动力学破坏与神经退行性过程发展之间已确立的联系。我们还讨论了针对神经元线粒体功能的不同治疗策略,这些策略已被提议作为有前景的神经保护治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6aa5/11641149/d3d4e2a51f9d/ijms-25-12855-g001.jpg

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