ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Necdin controls Foxo1 acetylation in hypothalamic arcuate neurons to modulate the thyroid axis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Prader-Willi syndrome protein necdin regulates the nucleocytoplasmic distribution and dopaminergic neuron development.Scientific reports · 2024Article
- Cloning, tissue expression and imprinting status analysis of the NDN gene in Dolang sheep.Molecular biology reports · 2024Article
- miR-183-5p promotes proliferation, invasion, and glycolysis of thyroid carcinoma cells by targeting FOXO1.Molecular and cellular biochemistry · 2022Article
- Loss of Function of the Neural Cell Adhesion Molecule NrCAM Regulates Differentiation, Proliferation and Neurogenesis in Early Postnatal Hypothalamic Tanycytes.Frontiers in neuroscience · 2022Article
- Necdin: A purposive integrator of molecular interaction networks for mammalian neuron vitality.Genes to cells : devoted to molecular & cellular mechanisms · 2021Review
- Necdin regulates BMAL1 stability and circadian clock through SGT1-HSP90 chaperone machinery.Nucleic acids research · 2020Article
- Hypothalamic NADBiomolecules · 2020Review
- Acupuncture Targeting SIRT1 in the Hypothalamic Arcuate Nucleus Can Improve Obesity in High-Fat-Diet-Induced Rats with Insulin Resistance via an Anorectic Effect.Obesity facts · 2020Article
- Role of genomic imprinting in mammalian development.Journal of biosciences · 2020Review
- Preclinical Testing in Translational Animal Models of Prader-Willi Syndrome: Overview and Gap Analysis.Molecular therapy. Methods & clinical development · 2019Review
- New Perspectives on Genomic Imprinting, an Essential and Multifaceted Mode of Epigenetic Control in the Developing and Adult Brain.Annual review of neuroscience · 2016Review
- Promotion of mitochondrial biogenesis by necdin protects neurons against mitochondrial insults.Nature communications · 2016Article
- Molecular mechanisms of the suppression of axon regeneration by KLF transcription factors.Neural regeneration research · 2014Review
- Systemic regulation of mammalian ageing and longevity by brain sirtuins.Nature communications · 2014Review
- Article
- Necdin controls proliferation and apoptosis of embryonic neural stem cells in an oxygen tension-dependent manner.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- RNAs of the human chromosome 15q11-q13 imprinted region.Wiley interdisciplinary reviews. RNAReview
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The forkhead transcription factor Foxo1 regulates energy homeostasis by modulating gene expression in the hypothalamus. Foxo1 undergoes post-translational modifications such as phosphorylation and acetylation, which modulate its functional activities. Sirtuin1 (Sirt1), a nicotinamide adenine dinucleotide-dependent protein deacetylase, regulates the acetylation status of Foxo1 in mammalian cells. Necdin, a pleiotropic protein required for neuronal development and survival, interacts with both Sirt1 and p53 to facilitate p53 deacetylation. The necdin gene (Ndn), an imprinted gene transcribed only from the paternal allele, is strongly expressed in hypothalamic neurons. Here, we demonstrate that necdin controls the acetylation status of Foxo1 in vivo in hypothalamic arcuate neurons to modulate the thyroid function. Necdin forms a stable ternary complex with Sirt1 and Foxo1, diminishes Foxo1 acetylation, and suppresses the transcriptional activity of Foxo1 in vitro. Paternal Ndn mutant mice express high levels of acetylated Foxo1 and mRNAs encoding agouti-related protein and neuropeptide Y in the hypothalamus in vivo during the juvenile period. The mutant mice exhibit endocrine dysfunction characteristic of hypothalamic hypothyroidism. Chemically induced hyperthyroidism and hypothyroidism lead to hypothalamic responses similar to those under necdin-deficient and excessive conditions, respectively, suggesting that thyroid hormone serves as a negative regulator of this system. These results suggest that necdin regulates Foxo1 acetylation and neuropeptide gene expression in the arcuate neurons to modulate the hypothalamic-pituitary-thyroid axis during development.
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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.