The pathophysiology of fragile X (and what it teaches us about synapses)

Asha L. Bhakar, G̈ul D̈olen, Mark F. Bear

Research output: Contribution to journalReview articlepeer-review

Abstract

Fragile X is the most common known inherited cause of intellectual disability and autism, and it typically results from transcriptional silencing of FMR1 and loss of the encoded protein, FMRP (fragile X mental retardation protein). FMRP is an mRNA-binding protein that functions at many synapses to inhibit local translation stimulated bymetabotropic glutamate receptors (mGluRs) 1 and 5. Recent studies on the biology of FMRP and the signaling pathways downstream of mGluR1/5 have yielded deeper insight into how synaptic protein synthesis and plasticity are regulated by experience. This new knowledge has also suggested ways that altered signaling and synaptic function can be corrected in fragile X, and human clinical trials based on this information are under way.

Original languageEnglish (US)
Pages (from-to)417-443
Number of pages27
JournalAnnual review of neuroscience
Volume35
DOIs
StatePublished - Jul 2012

Keywords

  • FMRP
  • autism
  • long-term depression
  • mRNA translation
  • metabotropic glutamate receptor

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'The pathophysiology of fragile X (and what it teaches us about synapses)'. Together they form a unique fingerprint.

Cite this