New York University Center for Neural Science New York United States
We hypothesize that excessive cap-dependent translation is a causative factor in FXS. To test this hypothesis, we will 1 determine cortico-striatal synaptic composition, function, and plasticity in FXS model mice, and 2 determine whether altered cortico-striatal synaptic plasticity and repetitiveperseverative behaviors displayed by FXS model mice are reversed by novel cap-dependent translation inhibitors. Our studies will provide information concerning whether increased eIF4E-eIF4G interactions are a biological risk factor for ASD. Our studies should also provide important information concerning the role of upregulated cap-dependent translation in FXS, and could link FXS mechanistically at the level of cap-dependent translational control to TSC, and autistic patients with PTEN, CYFIP1 and EIF4E mutations. Moreover, the results of these studies would provide information for the design and use of compounds to therapeutically target eIF4E-eIF4G interactions and eIF4A for treating patients with FXS and other ASDs.