Excessive Cap-dependent Translation as a Molecular Mechanism Underlying ASD
Abstract
We hypothesize that excessive cap-dependent translation is a causative factor in autism spectrum disorder (ASD). To test this hypothesis, we have been studying transgenic mice that overexpress eIF4E have been testing the following specific aims: 1) to determine whether eIF4E transgenic mice display behaviors consistent with ASD, 2) to determine whether ASD-like behaviors displayed by eIF4E transgenic mice can be reversed by novel cap-dependent translation inhibitors, and 3) to determine whether eIF4E transgenic mice display cellular and molecular abnormalities due to excessive cap-dependent translation. mice. Our studies will provide information concerning whether overexpression of eIF4E is a biological risk factor for ASD. Our studies also will provide important information concerning the role of upregulated cap-dependent translation in ASD, and could link ASD mechanistically at the level of cap-dependent translational control to fragile X syndrome (FXS), tuberous sclerosis complex (TSC), and autistic patients with PTEN 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 ASD.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2013
- Accession Number
- ADA592185
Entities
People
- Eric Klann
Organizations
- New York University