alexa Autism-related deficits via dysregulated eIF4E-dependent translational control.
Neurology

Neurology

Autism-Open Access

Author(s): Gkogkas CG, Khoutorsky A, Ran I, Rampakakis E, Nevarko T,

Abstract Share this page

Abstract Hyperconnectivity of neuronal circuits due to increased synaptic protein synthesis is thought to cause autism spectrum disorders (ASDs). The mammalian target of rapamycin (mTOR) is strongly implicated in ASDs by means of upstream signalling; however, downstream regulatory mechanisms are ill-defined. Here we show that knockout of the eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2)-an eIF4E repressor downstream of mTOR-or eIF4E overexpression leads to increased translation of neuroligins, which are postsynaptic proteins that are causally linked to ASDs. Mice that have the gene encoding 4E-BP2 (Eif4ebp2) knocked out exhibit an increased ratio of excitatory to inhibitory synaptic inputs and autistic-like behaviours (that is, social interaction deficits, altered communication and repetitive/stereotyped behaviours). Pharmacological inhibition of eIF4E activity or normalization of neuroligin 1, but not neuroligin 2, protein levels restores the normal excitation/inhibition ratio and rectifies the social behaviour deficits. Thus, translational control by eIF4E regulates the synthesis of neuroligins, maintaining the excitation-to-inhibition balance, and its dysregulation engenders ASD-like phenotypes.
This article was published in Nature and referenced in Autism-Open Access

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • Neurology and Neurological Disorders
    July 17-18, 2017 Chicago, USA
  • International Conference on Social Sciences & Interdisciplinary Studies
    August 07-17 London, UK
  • 3rd International Conference on Autism
    Aug 21-22, 2017 Los Angeles, USA
  • 3rd International Conference on Epilepsy and Treatment
    September 01-17 Brussels, Belgium

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords