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From FMRP Function to Potential Therapies for Fragile X Syndrome

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Abstract

Fragile X syndrome (FXS) is caused by mutations in the fragile X mental retardation 1 (FMR1) gene. Most FXS cases occur due to the expansion of the CGG trinucleotide repeats in the 5′ un-translated region of FMR1, which leads to hypermethylation and in turn silences the expression of FMRP (fragile X mental retardation protein). Numerous studies have demonstrated that FMRP interacts with both coding and non-coding RNAs and represses protein synthesis at dendritic and synaptic locations. In the absence of FMRP, the basal protein translation is enhanced and not responsive to neuronal stimulation. The altered protein translation may contribute to functional abnormalities in certain aspects of synaptic plasticity and intracellular signaling triggered by Gq-coupled receptors. This review focuses on the current understanding of FMRP function and potential therapeutic strategies that are mainly based on the manipulation of FMRP targets and knowledge gained from FXS pathophysiology.

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Acknowledgments

This work was supported by research Grants from the National Institute of Health (MH093445) and FRAXA Research Foundation. I (Hongbing Wang) would like to pay special thanks to Dr. Richard Olsen who provided valuable advice and guidance and shared his enthusiasm in science during my graduate study.

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Authors and Affiliations

  1. Genetics Program, Michigan State University, East Lansing, MI, 48824, USA

    Ferzin Sethna

  2. College of Veterinary Medicine, Animal Medical Institute, Chonnam National University, Gwangju, 500-757, South Korea

    Changjong Moon

  3. Department of Physiology, Michigan State University, 567 Wilson Road, East Lansing, MI, 48824, USA

    Hongbing Wang

  4. Neuroscience Program, Michigan State University, East Lansing, MI, 48824, USA

    Hongbing Wang

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  1. Ferzin Sethna
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Correspondence to Hongbing Wang.

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Sethna, F., Moon, C. & Wang, H. From FMRP Function to Potential Therapies for Fragile X Syndrome. Neurochem Res 39, 1016–1031 (2014). https://doi.org/10.1007/s11064-013-1229-3

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