Lost in translation. New unexplored avenues for neuropsychopharmacology: epigenetics and microRNAs

Expert Opin Investig Drugs. 2013 Feb;22(2):217-33. doi: 10.1517/13543784.2013.749237. Epub 2012 Dec 19.

Abstract

Introduction: Mood and anxiety disorders are among the major causes of disability worldwide. Despite clear need for better therapies, efforts to develop novel drugs have been relatively unsuccessful. One major reason is lack of translation into neuropsychopharmacology of the impressive recent array of knowledge accrued by clinical and preclinical researches on the brain. Here focus is on epigenetics mechanisms, including microRNAs, which seem particularly promising for the identification of new targets for alternative pharmacological approaches.

Areas covered: First, the current knowledge about epigenetic mechanisms, including DNA methylation, posttranslational modification of histone proteins, focusing on histone methylation and acetylation, and posttranscriptional modulation of gene expression by microRNAs is described. Then evidence showing involvement of epigenetics and microRNAs in the pathophysiology of mood and anxiety disorders as well as evidence showing that some of the currently employed antidepressants and mood stabilizers also affect epigenetic and microRNA mechanisms are reviewed. Finally current evidence and novel approaches in favor of drugs regulating epigenetic and microRNA mechanisms as potential therapeutics for these disorders are discussed.

Expert opinion: Although still in its infancy, research investigating the effects of pharmacological modulation of epigenetic and microRNA mechanisms in neuropsychiatric disorders continues to provide encouraging findings, suggesting new avenues for treatment of mood and anxiety disorders.

Publication types

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

MeSH terms

  • Animals
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / genetics
  • Brain / drug effects
  • Brain / metabolism
  • DNA Methylation / drug effects
  • DNA Methylation / genetics
  • Epigenesis, Genetic / drug effects*
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • MicroRNAs / genetics*
  • Mood Disorders / drug therapy*
  • Mood Disorders / genetics
  • Neuropsychology*
  • Protein Processing, Post-Translational / drug effects
  • Psychotropic Drugs / administration & dosage
  • Psychotropic Drugs / adverse effects
  • Psychotropic Drugs / pharmacology
  • Psychotropic Drugs / therapeutic use*

Substances

  • Histones
  • MicroRNAs
  • Psychotropic Drugs