Fragile X Syndrome: A Disorder of Synaptic Protein Synthesis Dynamics

Abstract

Fragile X syndrome (FXS) is a developmental disorder resulting
from trinucleoide repeat expansion in the 5’UTR of FMR1 gene. Cognitive defi ciency and autistic features are among the common phenotypes of FXS. FMR1 gene codes for the protein FMRP, the absence of which leads to abnormal dendritic spine morphology and defective synaptic plasticity in animal models of fragile X syndrome. FMRP is a selective RNA binding protein and is shown to interact with a large number of mRNAs and micro-RNAs. FMRP modulates the translation of a subset of dendritic mRNAs in response to neuronal activity and plays a critical role in synaptic plasticity. Several models have been proposed to explain the mode of FMRP interaction with is target RNAs and mechanism of FMRP mediated translation regulation, while a comprehensive understanding of its function is still elusive. FMRP is also proposed to have a pivotal role in neuronal stem cell maintenance, neurogenesis and neuronal differentiation. The research on FMRP function has unearthed huge information about the intricate regulatory processes at the synapse and has highlighted importance of activity mediated translation in neurons. Progress in understanding the function of FMRP has helped to design targeted therapeutic approach for FXS and is leading the way for potential therapies for other autism spectrum disorders.