Molecular mechanisms of autism as a form of synaptic dysfunction
https://doi.org/10.18699/VJ16.217
Abstract
Autism spectrum disorders are a separate group of defects with a very high 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 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 an essential subunit for learning and memory. Interneuronal communicative relationships are plastic. The most prominent forms of synaptic plasticity are accompanied by changes in protein biosynthesis, both in neuron body and in dendrites. Protein biosynthesis or translation is a carefully regulated process, with a central role played by mTOR (mammalian or mechanistic target of rapamycin). Normally mTOR-regulated translation is slightly inhibited, and in most cases mutational damage to at least one of the links of the mTOR signaling pathway, increases translation and leads to impaired synaptic plasticity and behavior. Deregulation of the local translation in dendrites is connected with the following monogenic autism spectrum disorders: neurofibromatosis type 1, Noonan syndrome, Costello syndrome, Cowden syndrome, tuberous sclerosis, fragile X chromosome, syndrome, and Rett syndrome. The review considers the most important mutations leading to monogenic autism, as well as the possibility of a mechanism-based treatment of certain disorders of the autism spectrum.
About the Authors
E. A. Trifonova
Institute of Cytology and Genetics SB RAS
Russian Federation
Novosibirsk, Russia
Russian Federation
Novosibirsk, Russia
T. M. Khlebodarova
Institute of Cytology and Genetics SB RAS
Russian Federation
Novosibirsk, Russia
Russian Federation
Novosibirsk, Russia
N. E. Gruntenko
Institute of Cytology and Genetics SB RAS
Russian Federation
Novosibirsk, Russia
Russian Federation
Novosibirsk, Russia
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