title: Dynamic Akt/mTOR Signaling in Children with Autism Spectrum Disorder.
abstract: Autism spectrum disorder (ASD) is a behaviorally defined disorder affecting 1 in 68 children. Currently, there is no known cause for the majority of ASD cases nor are there physiological diagnostic tools or biomarkers to aid behavioral diagnosis. Whole-genome linkage studies, genome-wide association studies, copy number variation screening, and SNP analyses have identified several ASD candidate genes, but which vary greatly among individuals and family clusters, suggesting that a variety of genetic mutations may result in a common pathology or alter a common mechanistic pathway. The Akt/mammalian target of rapamycin (mTOR) pathway is involved in many cellular processes including synaptic plasticity and immune function that can alter neurodevelopment. In this study, we examined the activity of the Akt/mTOR pathway in cells isolated from children with ASD and typically developing controls. We observed higher activity of mTOR, extracellular receptor kinase, and p70S6 kinase and lower activity of glycogen synthase kinase 3 (GSK3)α and tuberin (TSC2) in cells from children with ASD. These data suggest a phosphorylation pattern indicative of higher activity in the Akt/mTOR pathway in children with general/idiopathic ASD and may suggest a common pathological pathway of interest for ASD.
authors.affiliation: The M.I.N.D. Institute, University of California Davis, Davis, CA, USA; Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, USA.
authors.forename: Charity
authors.initials: C
authors.lastname: Onore
authors.affiliation: The M.I.N.D. Institute, University of California Davis, Davis, CA, USA; Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, USA.
authors.forename: Houa
authors.initials: H
authors.lastname: Yang
authors.affiliation: The M.I.N.D. Institute, University of California Davis, Davis, CA, USA; Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, Davis, CA, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Van de Water
authors.affiliation: The M.I.N.D. Institute, University of California Davis, Davis, CA, USA; Department of Medical Microbiology and Immunology, University of California Davis, Davis, CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Ashwood
keywords: T cells; autism; mTOR; phosphorylation; signaling