Dysregulation and restoration of translational homeostasis in fragile X syndrome

Nat Rev Neurosci. 2015 Oct;16(10):595-605. doi: 10.1038/nrn4001. Epub 2015 Sep 9.


Fragile X syndrome (FXS), the most-frequently inherited form of intellectual disability and the most-prevalent single-gene cause of autism, results from a lack of fragile X mental retardation protein (FMRP), an RNA-binding protein that acts, in most cases, to repress translation. Multiple pharmacological and genetic manipulations that target receptors, scaffolding proteins, kinases and translational control proteins can rescue neuronal morphology, synaptic function and behavioural phenotypes in FXS model mice, presumably by reducing excessive neuronal translation to normal levels. Such rescue strategies might also be explored in the future to identify the mRNAs that are critical for FXS pathophysiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Fragile X Mental Retardation Protein / biosynthesis
  • Fragile X Mental Retardation Protein / genetics*
  • Fragile X Syndrome / genetics*
  • Fragile X Syndrome / physiopathology
  • Gene Expression
  • Homeostasis / genetics*
  • Humans
  • Mice
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics


  • RNA, Messenger
  • Fragile X Mental Retardation Protein