Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132

Edbauer, Dieter; Neilson, Joel R.; Foster, Kelly A.; Wang, Chi-Fong; Seeburg, Daniel P.; Batterton, Matthew N.; Tada, Tomoko; Dolan, Bridget; Sharp, Phillip A.; Sheng, Morgan

doi:10.1016/j.neuron.2010.01.005

Cited by 676 publications

(651 citation statements)

References 67 publications

(108 reference statements)

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“…For instance, FMRP can recruit 4E-BP-like cytoplasmic Fmr-interacting protein 1 (CYFIP1) to repress the translation of target mRNAs (Napoli et al, 2008). Recent evidence indicate that FMRP can also repress the translation of cognate mRNAs through the association with miRNAs (Edbauer et al, 2010;Muddashetty et al, 2011) and through the reversible stalling of the ribosomes on polyribosomes containing FMRP-target mRNAs (Darnell et al, 2011).…”

Section: Trans-acting Factorsmentioning

confidence: 99%

BDNF-induced local protein synthesis and synaptic plasticity

2014

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a b s t r a c tBrain-derived neurotrophic factor (BDNF) is an important regulator of synaptic transmission and longterm potentiation (LTP) in the hippocampus and in other brain regions, playing a role in the formation of certain forms of memory. The effects of BDNF in LTP are mediated by TrkB (tropomyosin-related kinase B) receptors, which are known to be coupled to the activation of the Ras/ERK, phosphatidylinositol 3-kinase/Akt and phospholipase C-g (PLC-g) pathways. The role of BDNF in LTP is best studied in the hippocampus, where the neurotrophin acts at pre-and post-synaptic levels. Recent studies have shown that BDNF regulates the transport of mRNAs along dendrites and their translation at the synapse, by modulating the initiation and elongation phases of protein synthesis, and by acting on specific miRNAs. Furthermore, the effect of BDNF on transcription regulation may further contribute to long-term changes in the synaptic proteome. In this review we discuss the recent progress in understanding the mechanisms contributing to the short-and long-term regulation of the synaptic proteome by BDNF, and the role in synaptic plasticity, which is likely to influence learning and memory formation.This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.

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Section: Trans-acting Factorsmentioning

confidence: 99%

BDNF-induced local protein synthesis and synaptic plasticity

2014

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“…miR-132 is thought to function together with FMRP to regulate translation in dendrites. Dysregulation of miR-132 and its target genes is implicated in the pathophysiology of Fragile X syndrome (Edbauer et al, 2010) and schizophrenia .…”

Section: Micrornas In Epigenetic Remodelingmentioning

confidence: 99%

Epigenetic Mechanisms in Stroke and Epilepsy

Hwang

Aromolaran

Zukin

2012

Neuropsychopharmacol

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Epigenetic remodeling and modifications of chromatin structure by DNA methylation and histone modifications represent central mechanisms for the regulation of neuronal gene expression during brain development, higher-order processing, and memory formation. Emerging evidence implicates epigenetic modifications not only in normal brain function, but also in neuropsychiatric disorders. This review focuses on recent findings that disruption of chromatin modifications have a major role in the neurodegeneration associated with ischemic stroke and epilepsy. Although these disorders differ in their underlying causes and pathophysiology, they share a common feature, in that each disorder activates the gene silencing transcription factor REST (repressor element 1 silencing transcription factor), which orchestrates epigenetic remodeling of a subset of 'transcriptionally responsive targets' implicated in neuronal death. Although ischemic insults activate REST in selectively vulnerable neurons in the hippocampal CA1, seizures activate REST in CA3 neurons destined to die. Profiling the array of genes that are epigenetically dysregulated in response to neuronal insults is likely to advance our understanding of the mechanisms underlying the pathophysiology of these disorders and may lead to the identification of novel therapeutic strategies for the amelioration of these serious human conditions.

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“…In addition, FMRP is associated with the RISC complex (Jin et al, 2004), implying a role in microRNA-mediated translational control. In fact, recent studies indicate that FMRP regulates translation of certain cargo mRNAs via specific microRNAs targeted to their 3 0 UTR sequences (Edbauer et al, 2010;Muddashetty et al, 2011). Future studies will have to address whether and how FMRP regulates different steps during mRNA translation and if this regulation varies for specific targets.…”

Section: Fmrp: a Key Regulator Of Neuronal Functionmentioning

confidence: 99%

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

Groß

Berry‐Kravis

Bassell

2011

Neuropsychopharmacol

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Fragile X syndrome (FXS) is an inherited neurodevelopmental disease caused by loss of function of the fragile X mental retardation protein (FMRP). In the absence of FMRP, signaling through group 1 metabotropic glutamate receptors is elevated and insensitive to stimulation, which may underlie many of the neurological and neuropsychiatric features of FXS. Treatment of FXS animal models with negative allosteric modulators of these receptors and preliminary clinical trials in human patients support the hypothesis that metabotropic glutamate receptor signaling is a valuable therapeutic target in FXS. However, recent research has also shown that FMRP may regulate diverse aspects of neuronal signaling downstream of several cell surface receptors, suggesting a possible new route to more direct disease-targeted therapies. Here, we summarize promising recent advances in basic research identifying and testing novel therapeutic strategies in FXS models, and evaluate their potential therapeutic benefits. We provide an overview of recent and ongoing clinical trials motivated by some of these findings, and discuss the challenges for both basic science and clinical applications in the continued development of effective disease mechanism-targeted therapies for FXS.

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Regulation of Synaptic Structure and Function by FMRP-Associated MicroRNAs miR-125b and miR-132

Cited by 676 publications

References 67 publications

BDNF-induced local protein synthesis and synaptic plasticity

BDNF-induced local protein synthesis and synaptic plasticity

Epigenetic Mechanisms in Stroke and Epilepsy

Therapeutic Strategies in Fragile X Syndrome: Dysregulated mGluR Signaling and Beyond

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