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Neurological disorders

Targeting translation in autism

Nature Reviews Drug Discovery volume 12, page 21 (2013)Cite this article

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The eIF4F complex — which is composed of the cap-binding protein eIF4E, the RNA helicase eIF4A and the modular scaffolding protein eIF4G — is required for translation initiation of most mRNAs. eIF4F complex activity is regulated by 4EBPs, which repress eIF4E and disrupt complex formation. Recent studies have implicated a role for dysregulated eIF4E-dependent translation in ASD, so the authors set out to further investigate this hypothesis.

First, they knocked out 4EBP2 — the major 4EBP in the mammalian brain that has an important role in long-lasting synaptic plasticity, learning and memory — in mice, which would mimic the effects of eIF4E upregulation. These mice exhibited autistic-like behaviour, displaying social interaction deficits, altered communication and repetitive behaviours.

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ORIGINAL RESEARCH PAPER

  1. Gkogkas, C. G. et al. Autism-related deficits via dysregulated eIF4E-dependent translational control. Nature 21 Nov 2012 (doi:10.1038/nature11628)

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  1. Sarah Crunkhorn
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Crunkhorn, S. Targeting translation in autism. Nat Rev Drug Discov 12, 21 (2013). https://doi.org/10.1038/nrd3915

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