RNA methylations in depression, from pathological mechanism to therapeutic potential

Biochem Pharmacol. 2023 Sep:215:115750. doi: 10.1016/j.bcp.2023.115750. Epub 2023 Aug 16.

Abstract

Depression is caused by a variety of factors such as genetic factors, biological factors, and psychosocial factors, and the pathogenesis is complex. RNA methylations and related downstream signaling pathways influence a variety of biological mechanisms, including cell differentiation, tumorigenesis, sex determination, and stress response. In this work, we searched the PubMed, Web of Science, National Library of Science and Technology (NSTL), and ScienceDirect Online (SDOL) databases to summarize the biological roles of RNA methylations and their impact on the pathological mechanisms of depression. RNA methylations play a key role in the development of many diseases, and current research shows that RNA methylations are also closely linked to depression. RNA methylations in depression mainly involve "writers" (mediating the methylation modification process of RNAs), "erasers" (mediating the demethylation modification process of RNA methylation). Fat Mass and Obesity Associated (FTO) influences the development of depression by increasing body mass index (BMI), decreases the dopamine level, inhibits the adrenoceptor beta 2 (ADRB2)-c-Myc-sirt1 pathway, results in the m6A/m6Am dysregulation in brain, and may be involved in the pathogenesis of depression. The study of RNA methylations in depression has further deepened our understanding of the pathogenesis and development process of depression, provides new perspectives for the study of the pathological mechanism of depression, and provides new targets for the prevention and treatment of this disease.

Keywords: Depression; RNA demethyltransferase; RNA methylation; RNA methyltransferase; m6A.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • Brain
  • Carcinogenesis
  • Depression* / drug therapy
  • Depression* / genetics
  • Humans
  • Methylation
  • RNA*

Substances

  • RNA
  • FTO protein, human
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO