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线粒体质量控制:表观遗传特征与治疗策略。

Mitochondrial quality control: Epigenetic signatures and therapeutic strategies.

机构信息

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, 500037, India.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, Telangana, 500037, India.

出版信息

Neurochem Int. 2021 Sep;148:105095. doi: 10.1016/j.neuint.2021.105095. Epub 2021 Jun 8.

Abstract

Mitochondria are semi-autonomous organelle staging a crucial role in cellular stress response, energy metabolism and cell survival. Maintaining mitochondrial quality control is very important for its homeostasis. Pathological conditions such as oxidative stress and neurodegeneration, disrupt this quality control, and involvement of genetic and epigenetic materials in this disruption have been reported. These regulatory factors trigger mitochondrial imbalance, as seen in many neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Huntington's disease. The dynamic regulatory pathways i.e. mitophagy, biogenesis, permeability pore transitioning, fusion-fission are affected as a consequence and have been reviewed in this article. Moreover, several epigenetic mechanisms such as DNA methylation and histone modulation participating in such neurological disorders have also been discussed. Apart from it, therapeutic approaches targeting mitochondrial quality control have been tremendously explored showing ameliorative effects for these diseases, and have been discussed here with a novel perspective.

摘要

线粒体是半自主细胞器,在细胞应激反应、能量代谢和细胞存活中起着关键作用。维持线粒体的质量控制对于其动态平衡非常重要。氧化应激和神经退行性变等病理条件会破坏这种质量控制,并且已经报道了遗传和表观遗传物质在这种破坏中的参与。这些调节因子引发线粒体失衡,如在许多神经退行性疾病中所见,如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和亨廷顿病。这种动态调节途径,如自噬、生物发生、通透性孔转变、融合-分裂,受到影响,并在本文中进行了综述。此外,还讨论了参与这些神经疾病的几种表观遗传机制,如 DNA 甲基化和组蛋白修饰。除此之外,针对线粒体质量控制的治疗方法已经得到了极大的探索,显示出对这些疾病的改善作用,并在这里从一个新的角度进行了讨论。

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