ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Hypersensitivity to mGluR5 and ERK1/2 leads to excessive protein synthesis in the hippocampus of a mouse model of fragile X syndrome.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 254 papers.
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Who cites it
254 citing papers in PubMed, 384 citations in OpenAlex.
- Effects of AFQ056 on language learning in fragile X syndrome.The Journal of clinical investigation · 2023Trial
- Controlled trial of lovastatin combined with an open-label treatment of a parent-implemented language intervention in youth with fragile X syndrome.Journal of neurodevelopmental disorders · 2020Trial
- The Role of the Immunoglobulin Superfamily of Cell Adhesion Molecules in Intellectual Disability.Cells · 2026Review
- Neonatal expression of human FMRP isoform corrects cortical deficits and improves behavior in a mouse model of fragile X syndrome.Molecular therapy. Nucleic acids · 2026Article
- Impaired behavioral inhibition in Fmr1 KO mice is linked to disrupted visual cortex theta oscillations.Cell reports · 2026Article
- Impaired Activity-Regulated Proteostasis: A Shared Mechanism in Neurodevelopmental Disorders.Biological psychiatry · 2026Review
- Article
- Contribution of astrocytic calcium signaling to auditory hypersensitivity in a mouse model of fragile X syndrome.Neurobiology of disease · 2026Article
- Dysfunctional synaptic competition at dendritic spines in Fragile X syndrome.bioRxiv : the preprint server for biology · 2026Article
- Loss of Necdin causes social deficit and aberrant synaptic function through destabilization of SynGAP.Molecular psychiatry · 2026Article
- Altered Auditory Maturation in Fragile X Syndrome and Its Involvement in Audiogenic Seizure Susceptibility.Autism research : official journal of the International Society for Autism Research · 2026Article
- Cell-intrinsic mechanisms underlying spontaneous activity in the mouse visual cortical slice: implications for fragile X pathophysiology.Journal of neurophysiology · 2026Article
- GABAergic neurons exhibit subtype-specific changes in the developing somatosensory cortex of a rat model of Fragile X Syndrome.Frontiers in neuroscience · 2026Article
- Cell Type-Specific mTORC1 Signaling and Translational Control in Synaptic Plasticity and Memory.Journal of neurochemistry · 2025Review
- Sertraline treatment prevents motor dysfunction in a Huntington's disease mouse model and functional decline in patients.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Article
- Interaction between neuromuscular junction metabolic requirements in fragile X syndrome and glycogen storage disease models.Disease models & mechanisms · 2025Article
- Loss of FMRP in microglia promotes degeneration of parvalbumin neurons and audiogenic seizures via progranulin insufficiency.bioRxiv : the preprint server for biology · 2025Article
- Early life seizures chronically disrupt L-type voltage gated calcium channel regulation of mGluR mediated long term depression via interactions with protein phosphatase 2A.Neurobiology of disease · 2025Article
- Article
194 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Fragile X syndrome (FXS) is caused by loss of the FMR1 gene product FMRP (fragile X mental retardation protein), a repressor of mRNA translation. According to the metabotropic glutamate receptor (mGluR) theory of FXS, excessive protein synthesis downstream of mGluR5 activation causes the synaptic pathophysiology that underlies multiple aspects of FXS. Here, we use an in vitro assay of protein synthesis in the hippocampus of male Fmr1 knock-out (KO) mice to explore the molecular mechanisms involved in this core biochemical phenotype under conditions where aberrant synaptic physiology has been observed. We find that elevated basal protein synthesis in Fmr1 KO mice is selectively reduced to wild-type levels by acute inhibition of mGluR5 or ERK1/2, but not by inhibition of mTOR (mammalian target of rapamycin). The mGluR5-ERK1/2 pathway is not constitutively overactive in the Fmr1 KO, however, suggesting that mRNA translation is hypersensitive to basal ERK1/2 activation in the absence of FMRP. We find that hypersensitivity to ERK1/2 pathway activation also contributes to audiogenic seizure susceptibility in the Fmr1 KO. These results suggest that the ERK1/2 pathway, and other neurotransmitter systems that stimulate protein synthesis via ERK1/2, represent additional therapeutic targets for FXS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.