scholarly journals Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions

2021 ◽  
Vol 15 ◽  
Author(s):  
Snow Bach ◽  
Stephen Shovlin ◽  
Michael Moriarty ◽  
Barbara Bardoni ◽  
Daniela Tropea
Keyword(s):  
Fragile X Syndrome ◽  
Rett Syndrome ◽  
Rna Binding ◽  
Fragile X ◽  
Binding Protein ◽  
Synaptic Function ◽  
Synaptic Proteins ◽  
Large Set ◽  
Molecular Signaling ◽  
Cpg Dinucleotides

Rett syndrome (RTT) and Fragile X syndrome (FXS) are two monogenetic neurodevelopmental disorders with complex clinical presentations. RTT is caused by mutations in the Methyl-CpG binding protein 2 gene (MECP2) altering the function of its protein product MeCP2. MeCP2 modulates gene expression by binding methylated CpG dinucleotides, and by interacting with transcription factors. FXS is caused by the silencing of the FMR1 gene encoding the Fragile X Mental Retardation Protein (FMRP), a RNA binding protein involved in multiple steps of RNA metabolism, and modulating the translation of thousands of proteins including a large set of synaptic proteins. Despite differences in genetic etiology, there are overlapping features in RTT and FXS, possibly due to interactions between MeCP2 and FMRP, and to the regulation of pathways resulting in dysregulation of common molecular signaling. Furthermore, basic physiological mechanisms are regulated by these proteins and might concur to the pathophysiology of both syndromes. Considering that RTT and FXS are disorders affecting brain development, and that most of the common targets of MeCP2 and FMRP are involved in brain activity, we discuss the mechanisms of synaptic function and plasticity altered in RTT and FXS, and we consider the similarities and the differences between these two disorders.

RNAs That Interact with the Fragile X Syndrome RNA Binding Protein FMRP

2000 ◽  
Vol 275 (3) ◽  
pp. 973-980 ◽  
Author(s):  
Ying Ju Sung ◽  
James Conti ◽  
Julia R. Currie ◽  
W.Ted Brown ◽  
Robert B. Denman
Keyword(s):  
Fragile X Syndrome ◽  
Rna Binding ◽  
Fragile X ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals The Conserved, Disease-Associated RNA Binding Protein dNab2 Interacts with the Fragile X Protein Ortholog in Drosophila Neurons

Cell Reports ◽  
2017 ◽  
Vol 20 (6) ◽  
pp. 1372-1384 ◽  
Author(s):  
Rick S. Bienkowski ◽  
Ayan Banerjee ◽  
J. Christopher Rounds ◽  
Jennifer Rha ◽  
Omotola F. Omotade ◽  
...  
Keyword(s):  
Rna Binding ◽  
Fragile X ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
X Protein

Corrigendum to “Modulation of dendritic spines and synaptic function by Rac1: A possible link to fragile X syndrome pathology” [Brain Res. 1399 (2011) 79–95]

2011 ◽  
Vol 1423 ◽  
pp. 114-115
Author(s):  
Odelia Y.N. Bongmba ◽  
Luis A. Martinez ◽  
Mary E. Elhardt ◽  
Karlis Butler ◽  
Maria V. Tejada-Simon
Keyword(s):  
Fragile X Syndrome ◽  
Dendritic Spines ◽  
Fragile X ◽  
Synaptic Function

scholarly journals Aberrant Rac1-cofilin signaling mediates defects in dendritic spines, synaptic function, and sensory perception in fragile X syndrome

2017 ◽  
Vol 10 (504) ◽  
pp. eaan0852 ◽  
Author(s):  
Alexander Pyronneau ◽  
Qionger He ◽  
Jee-Yeon Hwang ◽  
Morgan Porch ◽  
Anis Contractor ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Dendritic Spines ◽  
Fragile X ◽  
Sensory Perception ◽  
Synaptic Function

scholarly journals FMRP promotes RNA localization to neuronal projections through interactions between its RGG domain and G-quadruplex RNA sequences

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Raeann Goering ◽  
Laura I Hudish ◽  
Bryan B Guzman ◽  
Nisha Raj ◽  
Gary J Bassell ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Fragile X ◽  
Rna Localization ◽  
Null Mouse ◽  
Rna Sequences ◽  
Rna Molecules ◽  
G Quadruplex

The sorting of RNA molecules to subcellular locations facilitates the activity of spatially restricted processes. We have analyzed subcellular transcriptomes of FMRP-null mouse neuronal cells to identify transcripts that depend on FMRP for efficient transport to neurites. We found that these transcripts contain an enrichment of G-quadruplex sequences in their 3′ UTRs, suggesting that FMRP recognizes them to promote RNA localization. We observed similar results in neurons derived from Fragile X Syndrome patients. We identified the RGG domain of FMRP as important for binding G-quadruplexes and the transport of G-quadruplex-containing transcripts. Finally, we found that the translation and localization targets of FMRP were distinct and that an FMRP mutant that is unable to bind ribosomes still promoted localization of G-quadruplex-containing messages. This suggests that these two regulatory modes of FMRP may be functionally separated. These results provide a framework for the elucidation of similar mechanisms governed by other RNA-binding proteins.

scholarly journals FMRP(1–297)-tat restores ion channel and synaptic function in a model of Fragile X syndrome

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xiaoqin Zhan ◽  
Hadhimulya Asmara ◽  
Ning Cheng ◽  
Giriraj Sahu ◽  
Eduardo Sanchez ◽  
...  
Keyword(s):  
Ion Channel ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Synaptic Function

scholarly journals New Targeted Treatments for Fragile X Syndrome

2019 ◽  
Vol 15 (4) ◽  
pp. 251-258 ◽  
Author(s):  
Dragana Protic ◽  
Maria J. Salcedo-Arellano ◽  
Jeanne Barbara Dy ◽  
Laura A. Potter ◽  
Randi J. Hagerman
Keyword(s):  
Mental Retardation ◽  
Intellectual Disability ◽  
Fragile X Syndrome ◽  
Behavioral Problems ◽  
Rna Binding ◽  
Fragile X ◽  
Symptomatic Treatment ◽  
Fmr1 Gene ◽  
Fragile X Mental Retardation ◽  
Cgg Repeats

Fragile X Syndrome (FXS) is the most common cause of inherited intellectual disability with prevalence rates estimated to be 1:5,000 in males and 1:8,000 in females. The increase of >200 Cytosine Guanine Guanine (CGG) repeats in the 5’ untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene results in transcriptional silencing on the FMR1 gene with a subsequent reduction or absence of fragile X mental retardation protein (FMRP), an RNA binding protein involved in the maturation and elimination of synapses. In addition to intellectual disability, common features of FXS are behavioral problems, autism, language deficits and atypical physical features. There are still no currently approved curative therapies for FXS, and clinical management continues to focus on symptomatic treatment of comorbid behaviors and psychiatric problems. Here we discuss several treatments that target the neurobiological pathway abnormal in FXS. These medications are clinically available at present and the data suggest that these medications can be helpful for those with FXS.

scholarly journals A Drosophila model of Fragile X syndrome exhibits defects in phagocytosis by innate immune cells

2017 ◽  
Vol 216 (3) ◽  
pp. 595-605 ◽  
Author(s):  
Reed M. O’Connor ◽  
Elizabeth F. Stone ◽  
Charlotte R. Wayne ◽  
Emily V. Marcinkevicius ◽  
Matt Ulgherait ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Immune Cells ◽  
Rna Binding ◽  
Fragile X ◽  
The Body ◽  
Innate Immune ◽  
Drosophila Model ◽  
A Cell ◽  
Increased Sensitivity ◽  
The Brain

Fragile X syndrome, the most common known monogenic cause of autism, results from the loss of FMR1, a conserved, ubiquitously expressed RNA-binding protein. Recent evidence suggests that Fragile X syndrome and other types of autism are associated with immune system defects. We found that Drosophila melanogaster Fmr1 mutants exhibit increased sensitivity to bacterial infection and decreased phagocytosis of bacteria by systemic immune cells. Using tissue-specific RNAi-mediated knockdown, we showed that Fmr1 plays a cell-autonomous role in the phagocytosis of bacteria. Fmr1 mutants also exhibit delays in two processes that require phagocytosis by glial cells, the immune cells in the brain: neuronal clearance after injury in adults and the development of the mushroom body, a brain structure required for learning and memory. Delayed neuronal clearance is associated with reduced recruitment of activated glia to the site of injury. These results suggest a previously unrecognized role for Fmr1 in regulating the activation of phagocytic immune cells both in the body and the brain.

Sign in / Sign up

Export Citation Format

Share Document