DNA methylation and its implications and accessibility for neuropsychiatric therapeutics

Annu Rev Pharmacol Toxicol. 2015;55:591-611. doi: 10.1146/annurev-pharmtox-010814-124527. Epub 2014 Oct 17.

Abstract

In this review, we discuss the potential pharmacological targeting of a set of powerful epigenetic mechanisms: DNA methylation control systems in the central nervous system (CNS). Specifically, we focus on the possible use of these targets for novel future treatments for learning and memory disorders. We first describe several unique pharmacological attributes of epigenetic mechanisms, especially DNA cytosine methylation, as potential drug targets. We then present an overview of the existing literature regarding DNA methylation control pathways and enzymes in the nervous system, particularly as related to synaptic function, plasticity, learning and memory. Lastly, we speculate upon potential categories of CNS cognitive disorders that might be amenable to methylomic targeting.

Keywords: DNMT; Tet oxidase; cognitive disorders; cognitive enhancement; cytosine methylation; demethylation; epigenetics; learning; memory; neuropharmacology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Central Nervous System Agents / therapeutic use*
  • Cognition / drug effects
  • DNA Methylation / drug effects*
  • DNA Modification Methylases / antagonists & inhibitors
  • DNA Modification Methylases / chemistry
  • DNA Modification Methylases / metabolism
  • Drug Discovery / methods*
  • Enzyme Inhibitors / therapeutic use
  • Epigenesis, Genetic / drug effects*
  • Gene Silencing / drug effects
  • Humans
  • Memory / drug effects
  • Mental Disorders / drug therapy*
  • Mental Disorders / genetics
  • Mental Disorders / psychology
  • Molecular Targeted Therapy / methods*
  • Nucleic Acid Conformation
  • Protein Conformation
  • Structure-Activity Relationship

Substances

  • Central Nervous System Agents
  • Enzyme Inhibitors
  • DNA Modification Methylases