ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
Necdin regulates p53 acetylation via Sirtuin1 to modulate DNA damage response in cortical neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 2 of them syntheses that pooled it.
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Who cites it
80 citing papers in PubMed, 2 syntheses or guidelines pooled it, 159 citations in OpenAlex.
- Integrated multi-cohort transcriptional meta-analysis of neurodegenerative diseases.Acta neuropathologica communications · 2014Pooled it
- Recommendations for the investigation of animal models of Prader-Willi syndrome.Mammalian genome : official journal of the International Mammalian Genome Society · 2013Guideline
- Evaluation of the Impact of Micellar Formulation of Resveratrol on Neurotrophic Factors and Neuromodulatory Potential in Healthy Rats.Molecules (Basel, Switzerland) · 2026Article
- Loss of Necdin causes social deficit and aberrant synaptic function through destabilization of SynGAP.Molecular psychiatry · 2026Article
- Mechanistic Links Between the Gut Microbiome and Longevity Therapeutics.Biomedicines · 2026Review
- Mechanistic and preclinical evaluation of SIRT3 as a therapeutic target in melanoma.Journal of dermato-oncology · 2026Article
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- Harvesting Health: Phytochemicals in Cognitive Impairment Therapy.Central nervous system agents in medicinal chemistry · 2025Review
- Prader-Willi syndrome protein necdin regulates the nucleocytoplasmic distribution and dopaminergic neuron development.Scientific reports · 2024Article
- Integrating network pharmacology and experimental validation to investigate the effects and mechanism of Renshen Shouwu decoction for ameliorating Alzheimer's disease.Pharmaceutical biology · 2024Article
- Malignancies in Prader-Willi Syndrome: Results From a Large International Cohort and Literature Review.The Journal of clinical endocrinology and metabolism · 2023Review
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- Inflammation and immune cell abnormalities in intracranial aneurysm subarachnoid hemorrhage (SAH): Relevant signaling pathways and therapeutic strategies.Frontiers in immunology · 2022Review
- Synergistic association of resveratrol and histone deacetylase inhibitors as treatment in amyotrophic lateral sclerosis.Frontiers in pharmacology · 2022Review
- Oxidized GAPDH transfers S-glutathionylation to a nuclear protein Sirtuin-1 leading to apoptosis.Free radical biology & medicine · 2021Article
- Necdin: A purposive integrator of molecular interaction networks for mammalian neuron vitality.Genes to cells : devoted to molecular & cellular mechanisms · 2021Review
- Phospholipase D2 is a positive regulator of sirtuin 1 and modulates p53-mediated apoptosis via sirtuin 1.Experimental & molecular medicine · 2021Article
- SIRT1 Promotes Neuronal Fortification in Neurodegenerative Diseases through Attenuation of Pathological Hallmarks and Enhancement of Cellular Lifespan.Current neuropharmacology · 2021Review
- Article
- Sirtuins, brain and cognition: A review of resveratrol effects.IBRO reports · 2020Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sirtuin1 (Sirt1), a mammalian homolog of yeast Sir2, deacetylates the tumor suppressor protein p53 and attenuates p53-mediated cell death. Necdin, a p53-interacting protein expressed predominantly in postmitotic neurons, is a melanoma antigen family protein that promotes neuronal differentiation and survival. In mammals, the necdin gene (Ndn) is maternally imprinted, and mutant mice carrying mutated paternal Ndn show abnormalities of neuronal development. Here we report that necdin regulates the acetylation status of p53 via Sirt1 to suppress p53-dependent apoptosis in postmitotic neurons. Double-immunostaining analysis demonstrated that necdin colocalizes with Sirt1 in postmitotic neurons of mouse embryonic forebrain in vivo. Coimmunoprecipitation and in vitro binding analyses revealed that necdin interacts with both p53 and Sirt1 to potentiate Sirt1-mediated p53 deacetylation by facilitating their association. Primary cortical neurons prepared from paternal Ndn-deficient mice have high p53 acetylation levels and are sensitive to the DNA-damaging compounds camptothecin and hydrogen peroxide. Moreover, DNA transfection per se increases p53 acetylation and apoptosis in paternal Ndn-deficient neurons, whereas small interfering RNA-mediated p53 knockdown completely blocks these changes. However, Sirt1 knockdown increases both acetylated p53 level and apoptosis in wild-type neurons but fails to affect them in paternal Ndn-deficient neurons. In organotypic forebrain slice cultures treated with hydrogen peroxide, p53 is accumulated and colocalized with necdin and Sirt1 in cortical neurons. These results suggest that necdin downregulates p53 acetylation levels by forming a stable complex with p53 and Sirt1 to protect neurons from DNA damage-induced apoptosis.
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Registered trials
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