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

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

doi:10.1016/j.ibneur.2022.12.002

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

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

Authors

Yousef Rasmi^{1

2}, Ameneh Shokati^{3

4

5}, Amber Hassan^{6

7}, Shiva Gholizadeh-Ghaleh Aziz^{1

2}, Sepideh Bastani⁸, Ladan Jalali², Faeze Moradi⁹, Shahriar Alipour^{1

2

10}

Affiliations

¹ Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.
² Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.
³ Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
⁵ Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Dipartimento di Oncologia ed Emato-Oncologia, Università Degli Studi Di Milano, Via Festa del Perdono, Milano, Italy.
⁷ Laboratory of Translatonal Neurosciences, European School of Molecular Medicine, CEINGE Biotecnologie Avanzate S.c.a.rl.Via Gaetano Salvatore, Naples, Italy.
⁸ Stem cell and Regenerative Medicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
⁹ Tissue Engineering and Applied Cell Sciences Division, Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
¹⁰ Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.

Abstract

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.

Keywords: ADHD; Alzheimer’s; DNA methylation; Depression; Neurological disorders; Rett syndrome.

Publication types

Review