Pharmacological Reactivation of the Silenced <i>FMR1</i> Gene as a Targeted Therapeutic Approach for Fragile X Syndrome

Abstract

More than ~200 CGG repeats in the 5′ untranslated region of the FMR1 gene results in transcriptional silencing and the absence of the FMR1 encoded protein, FMRP. FMRP is an RNA-binding protein that regulates the transport and translation of a variety of brain mRNAs in an activity-dependent manner. The loss of FMRP causes dysregulation of many neuronal pathways and results in an intellectual disability disorder, fragile X syndrome (FXS). Currently, there is no effective treatment for FXS. In this review, we discuss reactivation of the FMR1 gene as a potential approach for FXS treatment with an emphasis on the use of small molecules to inhibit the pathways important for gene silencing.

Keywords

• fragile X syndrome
• gene reactivation
• RNA:DNA hybrid
• FMRP
• histone methylation
• DNA methylation
• <i>FMR1</i>
• PRC2