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MYST家族通过组蛋白或非组蛋白乙酰化在阿尔茨海默病发病机制中的作用。

Roles of the MYST Family in the Pathogenesis of Alzheimer's Disease via Histone or Non-histone Acetylation.

作者信息

Li Yuhong, Huang Hui, Zhu Man, Bai Hua, Huang Xiaowei

机构信息

1State Key Lab for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, Yunnan, China.

2Yunnan Institute of Tropical Crops, Jinghong, China.

出版信息

Aging Dis. 2021 Feb 1;12(1):132-142. doi: 10.14336/AD.2020.0329. eCollection 2021 Feb.

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and a major cause of death among elderly individuals. The etiology of AD involves a combination of genetic, environmental, and lifestyle factors. A number of epigenetic alterations in AD have recently been reported; for example, studies have found an increase in histone acetylation in patients with AD and the protective function of histone deacetylase inhibitors. The histone acetylases in the MYST family are involved in a number of key nuclear processes, such as gene-specific transcriptional regulation, DNA replication, and DNA damage response. Therefore, it is not surprising that they contribute to epigenetic regulation as an intermediary between genetic and environmental factors. MYST proteins also exert acetylation activity on non-histone proteins that are closely associated with the pathogenesis of AD. In this review, we summarized the current understanding of the roles of MYST acetyltransferases in physiological functions and pathological processes related to AD. Additionally, using published RNA-seq, ChIP-seq, and ChIP-chip data, we identified enriched pathways to further evaluate the correlation between MYST and AD. The recent research described in this review supports the importance of epigenetic modifications and the MYST family in AD, providing a basis for future functional studies.

摘要

阿尔茨海默病(AD)是最常见的神经退行性疾病之一,也是老年人死亡的主要原因。AD的病因涉及遗传、环境和生活方式等多种因素。最近有报道称AD存在多种表观遗传改变;例如,研究发现AD患者组蛋白乙酰化增加以及组蛋白去乙酰化酶抑制剂的保护作用。MYST家族中的组蛋白乙酰转移酶参与许多关键的核过程,如基因特异性转录调控、DNA复制和DNA损伤反应。因此,它们作为遗传和环境因素之间的中介参与表观遗传调控也就不足为奇了。MYST蛋白还对与AD发病机制密切相关的非组蛋白发挥乙酰化活性。在本综述中,我们总结了目前对MYST乙酰转移酶在与AD相关的生理功能和病理过程中作用的认识。此外,利用已发表的RNA测序、染色质免疫沉淀测序和染色质免疫沉淀芯片数据,我们确定了富集途径,以进一步评估MYST与AD之间的相关性。本综述中描述的最新研究支持了表观遗传修饰和MYST家族在AD中的重要性,为未来的功能研究提供了基础。

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