In an article entitled, “Autism-related deficits via dysregulated eIF4E-dependent translational control published on the 17thJan.’13 issue of Nature (493:371-377), Cristos G. Gkogkas and 15 other associates suggest that hyperconnectivity of neuronal circuits owe to increased synaptic protein synthesis causes autism spectrum disorders (ASDs). The investigators showed that the absence of the eukaryotic translation initiation factor 4E-binding protein 2 (4E-BP2) or eIF4E overexpression leads to increased translation of neuroligins (a type 1 membrane protein), which are postsynaptic proteins linked to ASDs.
A survey of the literature reveals that mice without the Eif4ebp2 gene shows autism-like symptoms such as poor social interaction, distorted communication and recurring behaviors. Furthermore, researchers found that the mice showing autism-like-symptoms were characterized by high levels of neuroligins. Mice that have the gene encoding 4E-BP2 (Eif4ebp2) knocked out exhibit an increased ratio of excitatory to inhibitory synaptic inputs and autistic-like behaviors. The striking observation was that only normalization of neuroligins 1 protein levels restores the usual excitation/ inhibition ratio and set right the social behavior deficits. Thus, translational control by eIF4E regulates the synthesis of neuroligins, maintaining the balance between excitation and inhibition balance, and its imbalance i.e., the impairment of a physiological regulatory mechanism produces ASD-like phenotypes.