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阿尔茨海默病相关的表观遗传改变:新的治疗靶点。

Alzheimer's Disease-Related Epigenetic Changes: Novel Therapeutic Targets.

机构信息

Genetics Department, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran.

Zoonoses Research Center, Pasteur Institute of Iran, Amol, Iran.

出版信息

Mol Neurobiol. 2024 Mar;61(3):1282-1317. doi: 10.1007/s12035-023-03626-y. Epub 2023 Sep 12.

Abstract

Aging is a significant risk factor for Alzheimer's disease (AD), although the precise mechanism and molecular basis of AD are not yet fully understood. Epigenetic mechanisms, such as DNA methylation and hydroxymethylation, mitochondrial DNA methylation, histone modifications, and non-coding RNAs (ncRNAs), play a role in regulating gene expression related to neuron plasticity and integrity, which are closely associated with learning and memory development. This review describes the impact of dynamic and reversible epigenetic modifications and factors on memory and plasticity throughout life, emphasizing their potential as target for therapeutic intervention in AD. Additionally, we present insight from postmortem and animal studies on abnormal epigenetics regulation in AD, as well as current strategies aiming at targeting these factors in the context of AD therapy.

摘要

衰老是阿尔茨海默病(AD)的一个重要风险因素,尽管 AD 的确切机制和分子基础尚未完全阐明。表观遗传机制,如 DNA 甲基化和羟甲基化、线粒体 DNA 甲基化、组蛋白修饰和非编码 RNA(ncRNA),在调节与神经元可塑性和完整性相关的基因表达中发挥作用,这些与学习和记忆的发展密切相关。本综述描述了动态和可逆的表观遗传修饰和因素对整个生命周期中记忆和可塑性的影响,强调了它们作为 AD 治疗中治疗干预靶点的潜力。此外,我们还介绍了 AD 中异常表观遗传调控的尸检和动物研究的新见解,以及当前针对 AD 治疗中这些因素的靶向策略。

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