Department of Pharmacology, Zhejiang University of Technology, Hangzhou 310014, China.
Int J Mol Sci. 2022 Aug 26;23(17):9703. doi: 10.3390/ijms23179703.
Mitochondrial epigenetic alterations are closely related to Alzheimer's disease (AD), which is described in this review. Reports of the alteration of mitochondrial DNA (mtDNA) methylation in AD demonstrate that the disruption of the dynamic balance of mtDNA methylation and demethylation leads to damage to the mitochondrial electron transport chain and the obstruction of mitochondrial biogenesis, which is the most studied mitochondrial epigenetic change. Mitochondrial noncoding RNA modifications and the post-translational modification of mitochondrial nucleoproteins have been observed in neurodegenerative diseases and related diseases that increase the risk of AD. Although there are still relatively few mitochondrial noncoding RNA modifications and mitochondrial nuclear protein post-translational modifications reported in AD, we have reason to believe that these mitochondrial epigenetic modifications also play an important role in the AD process. This review provides a new research direction for the AD mechanism, starting from mitochondrial epigenetics. Further, this review summarizes therapeutic approaches to targeted mitochondrial epigenetics, which is the first systematic summary of therapeutic approaches in the field, including folic acid supplementation, mitochondrial-targeting antioxidants, and targeted ubiquitin-specific proteases, providing a reference for therapeutic targets for AD.
线粒体表观遗传改变与阿尔茨海默病（AD）密切相关，本综述对此进行了描述。AD 中线粒体 DNA（mtDNA）甲基化改变的报道表明，mtDNA 甲基化和去甲基化的动态平衡破坏导致线粒体电子传递链损伤和线粒体生物发生受阻，这是研究最多的线粒体表观遗传改变。在神经退行性疾病和相关疾病中观察到线粒体非编码 RNA 修饰和线粒体核蛋白的翻译后修饰，这些改变增加了 AD 的风险。尽管在 AD 中报道的线粒体非编码 RNA 修饰和线粒体核蛋白翻译后修饰仍然相对较少，但我们有理由相信这些线粒体表观遗传修饰也在 AD 过程中发挥重要作用。本综述从线粒体表观遗传学角度为 AD 机制提供了新的研究方向。此外，本综述还总结了靶向线粒体表观遗传学的治疗方法，这是该领域第一个系统的治疗方法总结，包括叶酸补充、靶向线粒体的抗氧化剂和靶向泛素特异性蛋白酶，为 AD 的治疗靶点提供了参考。
