scholarly journals A Direct Role for FMRP in Activity-Dependent Dendritic mRNA Transport Links Filopodial-Spine Morphogenesis to Fragile X Syndrome

2008 ◽  
Vol 14 (6) ◽  
pp. 926-939 ◽  
Author(s):  
Jason B. Dictenberg ◽  
Sharon A. Swanger ◽  
Laura N. Antar ◽  
Robert H. Singer ◽  
Gary J. Bassell
Keyword(s):  
Fragile X Syndrome ◽  
Fragile X ◽  
Mrna Transport ◽  
Direct Role ◽  
Dendritic Mrna ◽  
Activity Dependent ◽  
Spine Morphogenesis

scholarly journals Altered steady state and activity-dependent de novo protein expression in fragile X syndrome

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Heather Bowling ◽  
Aditi Bhattacharya ◽  
Guoan Zhang ◽  
Danyal Alam ◽  
Joseph Z. Lebowitz ◽  
...  
Keyword(s):  
Steady State ◽  
Protein Expression ◽  
Fragile X Syndrome ◽  
De Novo ◽  
Fragile X ◽  
Activity Dependent

FMRP Modulates Activity-Dependent Spine Plasticity by Binding Cofilin1 mRNA and Regulating Localization and Local Translation

2019 ◽  
Vol 29 (12) ◽  
pp. 5204-5216 ◽  
Author(s):  
Jonas Feuge ◽  
Franziska Scharkowski ◽  
Kristin Michaelsen-Preusse ◽  
Martin Korte
Keyword(s):  
Fragile X Syndrome ◽  
Fragile X ◽  
Treatment Strategies ◽  
Actin Dynamics ◽  
Actin Remodeling ◽  
Dendritic Spine Morphology ◽  
Novel Treatment Strategies ◽  
Activity Dependent ◽  
Spine Plasticity

Abstract Multiple variants of intellectual disability, e.g., the Fragile X Syndrome are associated with alterations in dendritic spine morphology, thereby pointing to dysregulated actin dynamics during development and processes of synaptic plasticity. Surprisingly, although the necessity of spine actin remodeling was demonstrated repeatedly, the importance and precise role of actin regulators is often undervalued. Here, we provide evidence that structural and functional plasticity are severely impaired after NMDAR-dependent LTP in the hippocampus of Fmr1 KO mice. We can link these defects to an aberrant activity-dependent regulation of Cofilin 1 (cof1) as activity-dependent modulations of local cof1 mRNA availability, local cof1 translation as well as total cof1 expression are impaired in the absence of FMRP. Finally, we can rescue activity-dependent structural plasticity in KO neurons by mimicking the regulation of cof1 observed in WT cells, thereby illustrating the potential of actin modulators to provide novel treatment strategies for the Fragile X Syndrome.

scholarly journals Local Protein Synthesis and Spine Morphogenesis: Fragile X Syndrome and Beyond

2006 ◽  
Vol 26 (27) ◽  
pp. 7151-7155 ◽  
Author(s):  
A. W. Grossman ◽  
G. M. Aldridge ◽  
I. J. Weiler ◽  
W. T. Greenough
Keyword(s):  
Protein Synthesis ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Local Protein Synthesis ◽  
Spine Morphogenesis ◽  
Local Protein

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

2019 ◽  
Vol 9 (2) ◽  
pp. 39 ◽  
Author(s):  
Daman Kumari ◽  
Inbal Gazy ◽  
Karen Usdin
Keyword(s):  
Small Molecules ◽  
Fragile X Syndrome ◽  
Untranslated Region ◽  
Rna Binding ◽  
Fragile X ◽  
Rna Binding Protein ◽  
Fmr1 Gene ◽  
Dependent Manner ◽  
Cgg Repeats ◽  
Activity Dependent

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.

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