Targeting PI3K-AKT/mTOR signaling in the prevention of autism

Neurochem Int. 2021 Jul:147:105067. doi: 10.1016/j.neuint.2021.105067. Epub 2021 May 13.

Abstract

PI3K-AKT/mTOR signaling pathway represents an essential signaling mechanism for mammalian enzyme-related receptors in transducing signals or biological processes such as cell development, differentiation, cell survival, protein synthesis, and metabolism. Upregulation of the PI3K-AKT/mTOR signaling pathway involves many human brain abnormalities, including autism and other neurological dysfunctions. Autism is a neurodevelopmental disorder associated with behavior and psychiatric illness. This research-based review discusses the functional relationship between the neuropathogenic factors associated with PI3K-AKT/mTOR signaling pathway. Ultimately causes autism-like conditions associated with genetic alterations, neuronal apoptosis, mitochondrial dysfunction, and neuroinflammation. Therefore, inhibition of the PI3K-AKT/mTOR signaling pathway may have an effective therapeutic value for autism treatment. The current review also summarizes the involvement of PI3K-AKT/mTOR signaling pathway inhibitors in the treatment of autism and other neurodegenerative disorders.

Keywords: Apoptosis; Autism; Genetic dysfunction; PI3K-AKT; Serotonergic degeneration; mTOR.

Publication types

  • Review

MeSH terms

  • Animals
  • Autistic Disorder / prevention & control*
  • Humans
  • Phosphatidylinositol 3-Kinases / drug effects*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / drug effects*

Substances

  • Protein Kinase Inhibitors
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases