Smt. Kishoritai Bhoyar College of Pharmacy, New Kamptee- 441002, Nagpur, Maharashtra, India.
Department of Bioscience and Biotechnology, Sejong University, Gwangjin-gu, Seoul 05006, Republic of Korea.
Mitochondrion. 2024 Sep;78:101926. doi: 10.1016/j.mito.2024.101926. Epub 2024 Jun 27.
Mitochondria are singular cell organelles essential for many cellular functions, which includes responding to stress, regulating calcium levels, maintaining protein homeostasis, and coordinating apoptosis response. The vitality of cells, therefore, hinges on the optimal functioning of these dynamic organelles. Mitochondrial Quality Control Mechanisms (MQCM) play a pivotal role in ensuring the integrity and functionality of mitochondria. Perturbations in these mechanisms have been closely associated with the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Compelling evidence suggests that targeting specific pathways within the MQCM could potentially offer a therapeutic avenue for rescuing mitochondrial integrity and mitigating the progression of neurodegenerative diseases. The intricate interplay of cellular stress, protein misfolding, and impaired quality control mechanisms provides a nuanced understanding of the underlying pathology. Consequently, unravelling the specific MQCM dysregulation in neurodegenerative disorders becomes paramount for developing targeted therapeutic strategies. This review delves into the impaired MQCM pathways implicated in neurodegenerative disorders and explores emerging therapeutic interventions. By shedding light on pharmaceutical and genetic manipulations aimed at restoring MQCM efficiency, the discussion aims to provide insights into novel strategies for ameliorating the progression of neurodegenerative diseases. Understanding and addressing mitochondrial quality control mechanisms not only underscore their significance in cellular health but also offer a promising frontier for advancing therapeutic approaches in the realm of neurodegenerative disorders.
线粒体是一种单一的细胞细胞器,对许多细胞功能至关重要,包括对压力的反应、钙水平的调节、蛋白质平衡的维持以及细胞凋亡反应的协调。因此,细胞的活力取决于这些动态细胞器的最佳功能。线粒体质量控制机制(MQCM)在确保线粒体的完整性和功能方面起着关键作用。这些机制的紊乱与神经退行性疾病的发病机制密切相关,如帕金森病、阿尔茨海默病、亨廷顿病和肌萎缩侧索硬化症。有令人信服的证据表明,针对 MQCM 中的特定途径可能为挽救线粒体完整性和减轻神经退行性疾病的进展提供一种治疗途径。细胞应激、蛋白质错误折叠和受损的质量控制机制之间的复杂相互作用提供了对潜在病理学的细致理解。因此,揭示神经退行性疾病中特定的 MQCM 失调对于开发靶向治疗策略至关重要。本综述深入探讨了神经退行性疾病中涉及的受损 MQCM 途径,并探讨了新兴的治疗干预措施。通过阐明旨在恢复 MQCM 效率的药物和遗传操作,讨论旨在为改善神经退行性疾病的进展提供新的策略提供思路。了解和解决线粒体质量控制机制不仅突显了它们在细胞健康中的重要性,而且为神经退行性疾病领域的治疗方法提供了一个有前途的前沿领域。