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

Int J Mol Sci. 2022 Jan 16;23(2):967. 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.

Keywords: autism spectrum disorder (ASD); autoimmune disorders (AIDs); bioinformatics; genetics; mTOR signaling pathway; maternal autoantibody-related (MAR) ASD; maternal immune activation (MIA); pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS).

Publication types

  • Review

MeSH terms

  • Autism Spectrum Disorder / classification
  • Autism Spectrum Disorder / immunology
  • Autism Spectrum Disorder / metabolism
  • Autism Spectrum Disorder / pathology*
  • Autoantibodies / metabolism
  • Child
  • Computational Biology / methods
  • Female
  • Humans
  • Pregnancy
  • Prenatal Exposure Delayed Effects / classification
  • Prenatal Exposure Delayed Effects / immunology
  • Prenatal Exposure Delayed Effects / metabolism
  • Prenatal Exposure Delayed Effects / pathology*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Autoantibodies
  • MTOR protein, human
  • TOR Serine-Threonine Kinases