By: A M Suzuki, K Griesi-Oliveira, C de Oliveira Freitas Machado, E Vadasz, E C Zachi, M R Passos-Bueno and A L Sertie
Molecular Psychiatry
2015
Recent autism spectrum disorders (ASD) research supports a model wherein disinhibited mTORC1 signaling and dysregulated protein synthesis in neurons contribute to the clinical features of ASD, mainly through disturbances in synaptic connectivity and plasticity.1, 2 Most insights into this pathomechanism came from ASD-related monogenic syndromes caused by loss of function mutations in negative regulators of PI3K-mTOR pathway (such as TSC1/TSC2, tuberous sclerosis syndrome; FMR1, fragile-X syndrome).3, 4 In addition, it has been recently reported aberrant mTORC1-dependent translation in a mouse model for nonsyndromic ASD (eIF4E).5 However, functional studies addressing mTORC1-signaling activity in accessible sources of cells from patients with nonsyndromic ASD are lacking. In this study we have made use of the cultured stem cells from human exfoliated deciduous teeth (SHEDs) derived from nonsyndromic ASD patients, a model system that, albeit non-neural, we have recently shown to be suitable to explore dysregulated pathways and biological processes in ASD,6 to investigate this important and yet poorly explored question.
