Abnormal mTOR Activity in Pediatric Autoimmune Neuropsychiatric and MIA-Associated Autism Spectrum Disorders.

Ekaterina A Trifonova,Sergey A Lashin,Alex V Kochetov,Zakhar S Mustafin

doi:10.3390/ijms23020967

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by the early onset of communication and behavioral problems. ASD is highly heritable; however, environmental factors also play a considerable role in this disorder. A significant part of both syndromic and idiopathic autism cases could be attributed to disorders caused by mammalian target of rapamycin (mTOR)-dependent translation deregulation. This narrative review analyzes both bioinformatic and experimental evidence that connects mTOR signaling to the maternal autoantibody-related (MAR) autism spectrum and autoimmune neuropsychiatric disorders simultaneously. In addition, we reconstruct a network presenting the interactions between the mTOR signaling and eight MAR ASD genes coding for ASD-specific maternal autoantibody target proteins. The research discussed in this review demonstrates novel perspectives and validates the need for a subtyping of ASD on the grounds of pathogenic mechanisms. The utter necessity of designing ELISA-based test panels to identify all antibodies related to autism-like behavior is also considered.

Highlights

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by the early onset of communication problems, including verbal communication, stereotypical behavior, and restricted interests
The syndromic form of ASD includes syndromes caused by monogenic mutations that significantly increase the risk of developing autism, but each of them has additional features not associated with ASD
One of the genes causing such a littleknown syndrome is the mechanical target of rapamycin, serine/threonine kinase, a central component of two multiprotein complexes, mTORC1 and mTORC2, which differ in protein composition and substrates

Summary

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by the early onset of communication problems, including verbal communication, stereotypical behavior, and restricted interests. This review analyzes autoimmune disorders leading to autism-like behavior, their connections with abnormal mTOR activity, and approaches to their diagnosis for subsequent immunomodulatory therapy. Both poly (I: C) and LPS affect maternal cytokine signaling (e.g., interleukin-6), which, through the placenta, affects fetal brain development [13], blocking key pathways that prevent MIA-induced neurological and behavioral anomalies in ASD model systems [14].

Results

Conclusion