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Molecular mechanisms of autism as a form of synaptic dysfunction

  • Published:
Russian Journal of Genetics: Applied Research

Abstract

Autism spectrum disorders (ASDs) are a separate group of developmental disorders with a very large genetic component. Genetic screening has identified hundreds of mutations and other genetic variations associated with autism, and bioinformatic analysis of signaling pathways and gene networks has led to the understanding that many of these mutational changes are involved in the functioning of synapses. A synapse is a site of electrochemical communication between neurons and is a required subunit for learning and memory. Interneuronal communicative connections are plastic. The most prominent forms of synaptic plasticity are accompanied by changes in protein biosynthesis, both in the neuron body and in dendrites. Protein biosynthesis, or translation, is a finely regulated process, with the central role played by mTOR kinase (mammalian or mechanistic target of rapamycin). A mutational aberration in at least one of the links of the mTOR signaling pathway impairs the synaptic plasticity and behavior. The deregulation of local translation in dendrites is connected with the following monogenic ASDs: neurofibromatosis type 1, Noonan syndrome, Costello syndrome, Cowden syndrome, tuberous sclerosis, fragile X syndrome, and Rett syndrome (RS). The review considers the most important mutations leading to monogenic autism. The possibility of a mechanism-based treatment of certain ASDs is discussed.

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  1. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    E. A. Trifonova, T. M. Khlebodarova & N. E. Gruntenko

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Original Russian Text © E.A. Trifonova, T.M. Khlebodarova, N.E. Gruntenko, 2016, published in Vavilovskii Zhurnal Genetiki i Selektsii, 2016, Vol. 20, No. 6, pp. 959–967.

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Trifonova, E.A., Khlebodarova, T.M. & Gruntenko, N.E. Molecular mechanisms of autism as a form of synaptic dysfunction. Russ J Genet Appl Res 7, 869–877 (2017). https://doi.org/10.1134/S2079059717080020

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