From FMRP function to potential therapies for fragile X syndrome

Neurochem Res. 2014 Jun;39(6):1016-31. doi: 10.1007/s11064-013-1229-3. Epub 2013 Dec 18.

Abstract

Fragile X syndrome (FXS) is caused by mutations in the fragile X mental retardation 1 (FMR1) gene. Most FXS cases occur due to the expansion of the CGG trinucleotide repeats in the 5' un-translated region of FMR1, which leads to hypermethylation and in turn silences the expression of FMRP (fragile X mental retardation protein). Numerous studies have demonstrated that FMRP interacts with both coding and non-coding RNAs and represses protein synthesis at dendritic and synaptic locations. In the absence of FMRP, the basal protein translation is enhanced and not responsive to neuronal stimulation. The altered protein translation may contribute to functional abnormalities in certain aspects of synaptic plasticity and intracellular signaling triggered by Gq-coupled receptors. This review focuses on the current understanding of FMRP function and potential therapeutic strategies that are mainly based on the manipulation of FMRP targets and knowledge gained from FXS pathophysiology.

Publication types

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

MeSH terms

  • Animals
  • Drug Delivery Systems / methods
  • Fragile X Mental Retardation Protein / physiology*
  • Fragile X Syndrome / drug therapy
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / physiopathology*
  • Humans
  • Minocycline / administration & dosage
  • Protein Biosynthesis / drug effects
  • Protein Biosynthesis / physiology*

Substances

  • FMR1 protein, human
  • Fragile X Mental Retardation Protein
  • Minocycline