| Autism is a neurodevelopmental disorder that affects 1% of the population and causes deficits in social interaction, communication and behavioral flexibility. Autism is highly heritable, but multiple genes appear to contribute to the disorder. Recent research indicates that several genes in the phosphoinositide-3-kinase (PI3K) signaling pathway contribute to autism risk (Levitt & Campbell, 2009, Journal of Clinical Investigation, 119: 747). Moreover, many neurodevelopmental syndromes like neurofibromatosis, tuberous sclerosis and Fragile X, having significant rates of co-occurring autism, show evident disruption in the signaling of the PI3K pathway.;Dysfunction of the PI3K pathway signaling has been described extensively in cancer cells, and although it has received substantial implications in ASD, it has not been studied in brain cells. To begin to understand how PI3K signaling is disrupted in autism, we propose experiments in human neuronal cell lines that use the tools developed by years of cancer research. The cancer literature indicates this pathway can be manipulated by the use of pharmacological inhibitors of PI3K. We plan to study the effect of an array of inhibitors of PI3K as well as its individual subunits on the cellular signaling pathway of these neuronal cell lines. |
