{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Udagawa T"],"funding":["NIMH NIH HHS","NINDS NIH HHS","NIGMS NIH HHS"],"pagination":["1473-7"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3823751"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(11)"],"pubmed_abstract":["Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice rescued working memory deficits, demonstrating reversal of this FXS phenotype. Finally, we find that FMRP and CPEB1 balance translation at the level of polypeptide elongation. Our results suggest that disruption of translational homeostasis is causal for FXS and that the maintenance of this homeostasis by FMRP and CPEB1 is necessary for normal neurologic function."],"journal":["Nature medicine"],"pubmed_title":["Genetic and acute CPEB1 depletion ameliorate fragile X pathophysiology."],"pmcid":["PMC3823751"],"funding_grant_id":["NS079415","GM46779","R01 NS079415","F32GM095060","MH086509","R01 GM046779","R01 MH086509","F32 GM095060"],"pubmed_authors":["Nagaoka K","Lorenz LJ","Alarcon JM","Chattarji S","Ivshina M","Farny NG","Hurt JA","Klann E","Akbarian S","Jakovcevski M","Bassell GJ","Kaphzan H","Udagawa T","Anilkumar S","Nalavadi VC","Richter JD"],"additional_accession":[]},"is_claimable":false,"name":"Genetic and acute CPEB1 depletion ameliorate fragile X pathophysiology.","description":"Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice rescued working memory deficits, demonstrating reversal of this FXS phenotype. Finally, we find that FMRP and CPEB1 balance translation at the level of polypeptide elongation. Our results suggest that disruption of translational homeostasis is causal for FXS and that the maintenance of this homeostasis by FMRP and CPEB1 is necessary for normal neurologic function.","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013 Nov","modification":"2025-04-04T00:03:58.956Z","creation":"2019-03-27T03:08:20Z"},"accession":"S-EPMC3823751","cross_references":{"pubmed":["24141422"],"doi":["10.1038/nm.3353"]}}