ArticleEMBO reports2021
Infantile spasms-linked Nedd4-2 mediates hippocampal plasticity and learning via cofilin signaling.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 6 citations in OpenAlex.
- Hyperfunction of PSD-95 leads to hyperexcitability and cognitive abnormalities in MEF2C haploinsufficiency.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- ATF4 Modulates Group 1 mGluR-Dependent molecular signaling, hippocampal plasticity and behavior.Molecular psychiatry · 2026Article
- E3 Ubiquitin Ligase Nedd4-2 Exacerbates Seizure-Induced Mitochondrial Defects in an Alzheimer's Disease Mouse Model.Journal of neurochemistry · 2026Article
- N-terminal α-amino SUMOylation promotes phosphorylation-independent cofilin-1 translocation to the mitochondrial matrix and induces apoptosis.Nature communications · 2025Article
- Hyperfunction of post-synaptic density protein 95 promotes seizure response in early-stage aβ pathology.EMBO reports · 2024Article
- mGluR7 allosteric modulator AMN082 corrects protein synthesis and pathological phenotypes in FXS.EMBO molecular medicine · 2024Article
- Nedd4-2 up-regulation is associated with ACE2 ubiquitination in hypertension.Cardiovascular research · 2023Article
- Tumor suppressor p53 modulates activity-dependent synapse strengthening, autism-like behavior and hippocampus-dependent learning.Molecular psychiatry · 2023Article
- Amyloid beta induces Fmr1-dependent translational suppression and hyposynchrony of neural activity via phosphorylation of eIF2α and eEF2.Journal of cellular physiology · 2022Article
- Infantile spasms-linked Nedd4-2 mediates hippocampal plasticity and learning via cofilin signaling.EMBO reports · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Individuals affected by infantile spasms (IS), such as those carrying mutations in an IS-linked gene, neural precursor cell expressed developmentally downregulated gene 4-like (Nedd4-2), exhibit developmental delays and learning disabilities, but the underlying mechanism is unknown. Using conditional Nedd4-2 knockout mice, we uncover that Nedd4-2 functions to maintain the excitatory synapses in hippocampal neurons and allows for late-phase long-term synaptic potentiation (L-LTP) at Schaffer collateral synapses in the hippocampus. We also find that Nedd4-2 is required for multiple forms of hippocampus-dependent learning and memory. Mechanistically, we show that loss of Nedd4-2 leads to a decrease in actin polymerization caused by reduced phosphorylation of the actin depolymerizing protein cofilin. A cell-permeable peptide promoting phosphorylation of endogenous cofilin in Nedd4-2 knockout neurons restores the number of hippocampal excitatory synapses and hippocampal L-LTP and partially restores hippocampus-dependent learning in mice. Taken together, our results reveal a novel mechanism underlying IS-associated learning disabilities and may provide information for future therapeutic strategies for IS.
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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.