Vol 57(2023) N 2 p. 235-244; DOI 10.1134/S0026893323020206
E.A. Trifonova1*, A.A. Kotliarova2, A.V. Kochetov1,3
Abnormal mTOR Signaling Pathway Activity in Autism Spectrum Disorders: Prospects of Mechanism-Based Therapy1Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia
2Research Institute of Clinical and Experimental Lymphology-Branch of the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630117 Russia
Received - 2022-07-27; Revised - 2022-09-05; Accepted - 2022-09-21
Autism spectrum disorder (ASD) is a developmental disorder characterized by the early onset of problems with communication, learning, and behavior. The syndromic form of ASD is caused by monogenic mutations. When it is not possible to find genetic or other known mechanisms, the term "idiopathic autism" is used. A significant part of both syndromic and idiopathic autism is associated with translational deregulation dependent on the mechanistic target of rapamycin (mTOR). In this review, we present both bioinformatic and experimental data that link the mTOR signaling pathway to maternal autoantibody related autism and childhood autoimmune neuropsychiatric disorders such as Sydenham's chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS). The need for ASD subtyping and the prospects of mechanism-based therapy with inhibitors of the mTOR signaling pathway are also discussed.
autism spectrum disorder, mTOR, bioinformatics, mechanism-based therapy, maternal immune activation, PANDAS, Sydenham's chorea