Abstract
GENERAL COMMENTARY article Front. Cell. Neurosci., 26 March 2013Sec. Cellular Neuropathology Volume 7 - 2013 | https://doi.org/10.3389/fncel.2013.00028
Highlights
The genetic defects in Autism spectrum disorders (ASDs) may interfere with synaptic protein synthesis
TSC1/TSC2, neurofibromatosis 1 (NF1), and Phosphatase and tensin homolog (PTEN) act as negative regulators of mammalian target of the rapamycin (mTOR) complex 1, which is activated by phosphoinositide-3 kinase (PI3K) pathway (Kelleher and Bear, 2008; Auerbach et al, 2011; Sawicka and Zukin, 2012) (Figure 1)
A hyperactivated mTOR complex 1 (mTORC1)–eIF4E pathway is linked to impaired synaptic plasticity in fragile X syndrome, an autistic disorder caused by lack of fragile X mental retardation protein (FMRP) due to mutation of the FMR1 gene (Wang et al, 2010; Auerbach et al, 2011; Santoro et al, 2012; Wang et al, 2012), suggesting that downstream mTOR signaling might be causally linked to ASDs
Summary
A hyperactivated mTORC1–eIF4E pathway is linked to impaired synaptic plasticity in fragile X syndrome, an autistic disorder caused by lack of fragile X mental retardation protein (FMRP) due to mutation of the FMR1 gene (Wang et al, 2010; Auerbach et al, 2011; Santoro et al, 2012; Wang et al, 2012), suggesting that downstream mTOR signaling might be causally linked to ASDs. Notably, one pioneering study has identified a mutation in the EIF4E promoter in autism families (Neves-Pereira et al, 2009), implying that deregulation of downstream mTOR signaling (eIF4E) could be a novel mechanism for ASDs. As an eIF4E repressor downstream of mTOR, 4E-BP2 has important roles in synaptic plasticity, learning and memory (Banko et al, 2005; Richter and Klann, 2009). Pharmacological inhibition of eIF4E rectifies social behavior deficits in Eif4ebp2 knockout mice (Gkogkas et al, 2013).
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