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Pharmacological Reactivation of the Silenced FMR1 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.

SUBMITTER: Kumari D

PROVIDER: S-EPMC6406686 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Kumari Daman D Gazy Inbal I Usdin Karen K

Brain sciences 20190212 2

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 fo ...[more]

PMID: 30759772

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Targeted Reactivation of FMR1 Transcription in Fragile X Syndrome Embryonic Stem Cells.

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