ArticleNature neuroscience2015
Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition.
Article in Nature neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 95 citations in OpenAlex.
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Beyond Neddylation Inhibition: X‑ray Structures Reveal Carbonic Anhydrase Isoform Selectivity of Pevonedistat.ACS medicinal chemistry letters · 2026Article
- Article
- Fetal Neuronal Vesicles in the Assessment of Perinatal Brain Dysfunction and Late-Onset Growth Restriction: A Pilot Study.International journal of molecular sciences · 2026Article
- The modifier matrix: emerging roles of ubiquitin-like proteins in Alzheimer's disease.Molecular neurodegeneration advances · 2026Review
- NEDD8, stress granules, and amyotrophic lateral sclerosis: unveiling the therapeutic potential of the NEDP1 protease.Essays in biochemistry · 2025Review
- Genetic regulators of neuronal survival across metabolic environments.bioRxiv : the preprint server for biology · 2025Article
- Regulation of UBC12 expression and protein neddylation by PINK1 suggests a primate-specific function.Zoological research · 2025Article
- Neddylation regulates the development and function of glutamatergic neurons.Communications biology · 2025Article
- Transcriptome-based screening in TARDBP/TDP-43 knock-in motor neurons identifies the NEDD8-activating enzyme inhibitor MLN4924.Scientific reports · 2025Article
- PSD-95 Protein: A Promising Therapeutic Target in Chronic Pain.Molecular neurobiology · 2025Review
- Non-Invasive Assessment of Neurogenesis Dysfunction in Fetuses with Early-Onset Growth Restriction Using Fetal Neuronal Exosomes Isolating from Maternal Blood: A Pilot Study.International journal of molecular sciences · 2025Article
- Blockade of neddylation through targeted inhibition of DCN1 alleviates renal fibrosis.Clinical science (London, England : 1979) · 2025Article
- Article
- NAE1-mediated neddylation coordinates ubiquitination regulation of meiotic recombination during spermatogenesis.Theranostics · 2025Article
- Article
- Influence of RNA circularity on Target RNA-Directed MicroRNA Degradation.Nucleic acids research · 2024Article
- Protein neddylation and its role in health and diseases.Signal transduction and targeted therapy · 2024Review
- Integrated analysis reveals the regulatory mechanism of the neddylation inhibitor MLN4924 on the metabolic dysregulation in rabbit granulosa cells.BMC genomics · 2024Article
- Pronucleotide Probes Reveal a Diverging Specificity for AMPylation vs UMPylation of Human and Bacterial Nucleotide Transferases.Biochemistry · 2024Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neddylation is a ubiquitylation-like pathway that controls cell cycle and proliferation by covalently conjugating Nedd8 to specific targets. However, its role in neurons, nonreplicating postmitotic cells, remains unexplored. Here we report that Nedd8 conjugation increased during postnatal brain development and is active in mature synapses, where many proteins are neddylated. We show that neddylation controls spine development during neuronal maturation and spine stability in mature neurons. We found that neddylated PSD-95 was present in spines and that neddylation on Lys202 of PSD-95 is required for the proactive role of the scaffolding protein in spine maturation and synaptic transmission. Finally, we developed Nae1(CamKIIα-CreERT2) mice, in which neddylation is conditionally ablated in adult excitatory forebrain neurons. These mice showed synaptic loss, impaired neurotransmission and severe cognitive deficits. In summary, our results establish neddylation as an active post-translational modification in the synapse regulating the maturation, stability and function of dendritic spines.
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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.