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

Daman Kumari; Inbal Gazy; Karen Usdin

doi:10.3390/brainsci9020039

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

Brain Sci. 2019 Feb 12;9(2):39. doi: 10.3390/brainsci9020039.

Authors

Daman Kumari¹, Inbal Gazy², Karen Usdin³

Affiliations

¹ Section on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. damank@niddk.nih.gov.
² Section on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. inbal.gazy@nih.gov.
³ Section on Gene Structure and Disease, Laboratory of Cell and Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ku@helix.nih.gov.

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: DNA methylation; FMR1; FMRP; PRC2; RNA:DNA hybrid; fragile X syndrome; gene reactivation; histone methylation.

Publication types

Review

Abstract

Publication types

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