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DNA甲基化在神经系统疾病和神经退行性疾病进展中的作用以及使用DNA甲基化抑制剂作为此类疾病治疗药物的前景。

The role of DNA methylation in progression of neurological disorders and neurodegenerative diseases as well as the prospect of using DNA methylation inhibitors as therapeutic agents for such disorders.

作者信息

Rasmi Yousef, Shokati Ameneh, Hassan Amber, Aziz Shiva Gholizadeh-Ghaleh, Bastani Sepideh, Jalali Ladan, Moradi Faeze, Alipour Shahriar

机构信息

Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.

Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

出版信息

IBRO Neurosci Rep. 2022 Dec 12;14:28-37. doi: 10.1016/j.ibneur.2022.12.002. eCollection 2023 Jun.

Abstract

UNLABELLED

Genome-wide studies related to neurological disorders and neurodegenerative diseases have pointed to the role of epigenetic changes such as DNA methylation, histone modification, and noncoding RNAs. DNA methylation machinery controls the dynamic regulation of methylation patterns in discrete brain regions.

OBJECTIVE

This review aims to describe the role of DNA methylation in inhibiting and progressing neurological and neurodegenerative disorders and therapeutic approaches

METHODS

A Systematic search of PubMed, Web of Science, and Cochrane Library was conducted for all qualified studies from 2000 to 2022.

RESULTS

For the current need of time, we have focused on the DNA methylation role in neurological and neurodegenerative diseases and the expression of genes involved in neurodegeneration such as Alzheimer's, Depression, and Rett Syndrome. Finally, it appears that the various epigenetic changes do not occur separately and that DNA methylation and histone modification changes occur side by side and affect each other. We focused on the role of modification of DNA methylation in several genes associated with depression (NR3C1, NR3C2, CRHR1, SLC6A4, BDNF, and FKBP5), Rett syndrome (MECP2), Alzheimer's, depression (APP, BACE1, BIN1 or ANK1) and Parkinson's disease (SNCA), as well as the co-occurring modifications to histones and expression of non-coding RNAs. Understanding these epigenetic changes and their interactions will lead to better treatment strategies.

CONCLUSION

This review captures the state of understanding of the epigenetics of neurological and neurodegenerative diseases. With new epigenetic mechanisms and targets undoubtedly on the horizon, pharmacological modulation and regulation of epigenetic processes in the brain holds great promise for therapy.

摘要

未标注

与神经系统疾病和神经退行性疾病相关的全基因组研究已指出表观遗传变化的作用,如DNA甲基化、组蛋白修饰和非编码RNA。DNA甲基化机制控制着离散脑区甲基化模式的动态调节。

目的

本综述旨在描述DNA甲基化在抑制和进展神经系统及神经退行性疾病中的作用以及治疗方法。

方法

对2000年至2022年期间所有合格研究在PubMed、科学网和考克兰图书馆进行了系统检索。

结果

鉴于当前的时间需求,我们重点关注了DNA甲基化在神经系统和神经退行性疾病中的作用以及与神经退行性变相关基因的表达,如阿尔茨海默病、抑郁症和雷特综合征。最后,各种表观遗传变化似乎并非单独发生,DNA甲基化和组蛋白修饰变化同时发生且相互影响。我们重点关注了DNA甲基化修饰在与抑郁症相关的几个基因(NR3C1、NR3C2、CRHR1、SLC6A4、BDNF和FKBP5)、雷特综合征(MECP2)、阿尔茨海默病、抑郁症(APP、BACE1、BIN1或ANK1)和帕金森病(SNCA)中的作用,以及组蛋白的同时修饰和非编码RNA的表达。了解这些表观遗传变化及其相互作用将带来更好的治疗策略。

结论

本综述阐述了对神经系统和神经退行性疾病表观遗传学的理解现状。随着新的表观遗传机制和靶点无疑即将出现,对大脑表观遗传过程的药理学调节和调控在治疗方面具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f11/9794904/602c197dba65/gr1.jpg

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