Repeat-Associated MicroRNAs Trigger Fragile X Mental Retardation-Like Syndrome in Zebrafish~!2008-10-29~!2008-11-12~!2008-11-26~!

Chang, Shin-Ju E.; Chang-Lin, Samantha; Chang, Donald C.; Chang, Chen Pu; Lin, Shi-Lung; Ying, Shao‐Yao

doi:10.2174/1876523800801010006

Cited by 4 publications

(1 citation statement)

References 30 publications

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“…MicroRNAs (miRNAs) are known as a class of small noncoding RNA molecules (19–23 nucleotides) that regulate almost 30% of genes at the post-transcriptional level in eukaryotic organisms [186]. Several studies have provided evidence of miRNA involvement in the pathogenesis of FXS by identifying and isolating several r(CGG)-derived miRNAs, including miR-fmr1-27 and miR-fmr1-42 in the zebrafish FXS model [187,188]. Their brain exhibits long dendrites and disconnected synapses, similar to those found in the human FXS hippocampal–neocortical junction [189].…”

Section: Additional Potential Biomarkersmentioning

confidence: 99%

Molecular Biomarkers in Fragile X Syndrome

Zafarullah

Tassone

2019

Brain Sciences

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Fragile X syndrome (FXS) is the most common inherited form of intellectual disability (ID) and a known monogenic cause of autism spectrum disorder (ASD). It is a trinucleotide repeat disorder, in which more than 200 CGG repeats in the 5’ untranslated region (UTR) of the fragile X mental retardation 1 (FMR1) gene causes methylation of the promoter with consequent silencing of the gene, ultimately leading to the loss of the encoded fragile X mental retardation 1 protein, FMRP. FMRP is an RNA binding protein that plays a primary role as a repressor of translation of various mRNAs, many of which are involved in the maintenance and development of neuronal synaptic function and plasticity. In addition to intellectual disability, patients with FXS face several behavioral challenges, including anxiety, hyperactivity, seizures, repetitive behavior, and problems with executive and language performance. Currently, there is no cure or approved medication for the treatment of the underlying causes of FXS, but in the past few years, our knowledge about the proteins and pathways that are dysregulated by the loss of FMRP has increased, leading to clinical trials and to the path of developing molecular biomarkers for identifying potential targets for therapies. In this paper, we review candidate molecular biomarkers that have been identified in preclinical studies in the FXS mouse animal model and are now under validation for human applications or have already made their way to clinical trials.

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Section: Additional Potential Biomarkersmentioning

confidence: 99%

Molecular Biomarkers in Fragile X Syndrome

Zafarullah

Tassone

2019

Brain Sciences

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microRNAs and Fragile X Syndrome

Lin¹

2015

Advances in Experimental Medicine and Biology

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Fragile X syndrome (FXS) is one of the major causes for autism and mental retardation in humans. The etiology of FXS is linked to the expansion of the CGG trinucleotide repeats, r(CGG), suppressing the fragile X mental retardation 1 (FMR1) gene on the X chromosome, resulting in a loss of fragile X mental retardation protein (FMRP) expression, which is required for regulating normal neuronal connectivity and plasticity. Recent studies have further identified that microRNAs are involved in the mechanisms underlying FXS pathogenesis at three different developmental stages. During early embryogenesis before the blastocyst stage, an embryonic stem cell (ESC)-specific microRNA, miR-302, interferes with FMR1 mRNA translation to maintain the stem cell status and inhibit neural development. After blastocyst, the downregulation of miR-302 releases FMRP synthesis and subsequently leads to neuronal development; yet, in FXS, certain r(CGG)-derived microRNAs, such as miR-fmr1s, are expressed and accumulated and then induce DNA hypermethylation on the FMR1 gene promoter regions, resulting in transcriptional inactivation of the FMR1 gene and the loss of FMRP. In normal neuronal development, FMRP is an RNA-binding protein responsible for interacting with miR-125 and miR-132 to regulate the signaling of Group 1 metabotropic glutamate receptor (mGluR1) and N-methyl-D-aspartate receptor (NMDAR), respectively, and consequently affecting synaptic plasticity. As a result, the loss of FMRP impairs these signaling controls and eventually causes FXS-associated disorders, such as autism and mental retardation. Based on these current findings, this chapter will summarize the etiological causes of FXS and further provides significant insights into the molecular mechanisms underlying microRNA-mediated FXS pathogenesis and the related therapy development.

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The Potential Role of miRNAs as Predictive Biomarkers in Neurodevelopmental Disorders

Juvale

Has

2021

J Mol Neurosci

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Repeat-Associated MicroRNAs Trigger Fragile X Mental Retardation-Like Syndrome in Zebrafish~!2008-10-29~!2008-11-12~!2008-11-26~!

Cited by 4 publications

References 30 publications

Molecular Biomarkers in Fragile X Syndrome

Molecular Biomarkers in Fragile X Syndrome

microRNAs and Fragile X Syndrome

The Potential Role of miRNAs as Predictive Biomarkers in Neurodevelopmental Disorders

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