A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders

Claudia Bagni, R. Suzanne Zukin

Research output: Contribution to journalReview article

16 Scopus citations

Abstract

Altered synaptic structure and function is a major hallmark of fragile X syndrome (FXS), autism spectrum disorders (ASDs), and other intellectual disabilities (IDs), which are therefore classified as synaptopathies. FXS and ASDs, while clinically and genetically distinct, share significant comorbidity, suggesting that there may be a common molecular and/or cellular basis, presumably at the synapse. In this article, we review brain architecture and synaptic pathways that are dysregulated in FXS and ASDs, including spine architecture, signaling in synaptic plasticity, local protein synthesis, (m)RNA modifications, and degradation. mRNA repression is a powerful mechanism for the regulation of synaptic structure and efficacy. We infer that there is no single pathway that explains most of the etiology and discuss new findings and the implications for future work directed at improving our understanding of the pathogenesis of FXS and related ASDs and the design of therapeutic strategies to ameliorate these disorders. ASDs and comorbid diseases such as FXS are caused by altered synaptic structure and connectivity. Bagni and Zukin review the construction and elimination of synapses: mild alterations in these pathways affect the equilibrium during development and cause the disease.

Original languageEnglish (US)
Pages (from-to)1070-1088
Number of pages19
JournalNeuron
Volume101
Issue number6
DOIs
StatePublished - Mar 20 2019

Keywords

  • ASDs
  • ERK
  • FMRP
  • FXS
  • MNK
  • TSC
  • mGluRs
  • mRNA metabolism
  • mTOR
  • synaptopathies

ASJC Scopus subject areas

  • Neuroscience(all)

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