The Department of Biomedicine

BBB seminar: Christos G. Gkogkas

Regulation of neuronal translation in Autism Spectrum Disorders

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Christos G. Gkogkas
Centre for Integrative Physiology and Patrick Wild Centre, University of Edinburgh, UK

Translation of mRNAs, also termed protein synthesis, relies upon an intricate molecular network, whose dysregulation can lead to pathological conditions like cancer, viral infections, neurodegeneration and neurodevelopmental diseases like Autism Spectrum Disorders (ASDs). ASDs encompass an ensemble of unique behaviours within three domains: social interaction, communication and restricted/repetitive/stereotyped behaviours. Our results show for the first time that exaggerated cap-dependent translation can lead to ASD-like behaviours in mice. These behaviours are concomitant with an imbalance of excitatory to inhibitory synaptic transmission, and increased translation of a subset of brain-specific mRNAs. Using pharmacological blockade of translation or gene therapy, targeting specific mRNAs, we were able to reverse ASD-like behaviours in mice. These results open new avenues for the development of strategies to modulate ASD-associated behaviours and further our understanding of the molecular underpinning of neurodevelopmental disorders.

Chairperson: Clive R. Bramham, Department of Biomedicine