ArticleBiochimica et biophysica acta2011
Tumor necrosis factor-alpha regulates the Hypocretin system via mRNA degradation and ubiquitination.
Article in Biochimica et biophysica acta, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 55 citations in OpenAlex.
- SARS-CoV-2 infection is associated with hypothalamic orexin suppression and persistent cortical NeuN attenuation.Journal of neuroinflammation · 2026Article
- Genetic associations between orexin genes and phenotypes related to behavioral regulation in humans, including substance use.Molecular psychiatry · 2025Article
- Stress-Induced Sleep Dysregulation: The Roles of Astrocytes and Microglia in Neurodegenerative and Psychiatric Disorders.Biomedicines · 2025Review
- Protective role of aconitate decarboxylase 1 in neuroinflammation-induced dysfunctions of the paraventricular thalamus and sleepiness.Communications biology · 2024Article
- Inclusion of hypocretin-1 improved performance of poor sleep quality prediction for elderly patients with acute ischemic stroke: a prospective cohort study.Frontiers in aging neuroscience · 2024Article
- Orexins in apoptosis: a dual regulatory role.Frontiers in cellular neuroscience · 2024Review
- Autocrine positive feedback of tumor necrosis factor from activated microglia proposed to be of widespread relevance in chronic neurological disease.Pharmacology research & perspectives · 2023Review
- Repeat mild traumatic brain injuries (RmTBI) modify nociception and disrupt orexinergic connectivity within the descending pain pathway.The journal of headache and pain · 2023Article
- Epigenetic silencing of selected hypothalamic neuropeptides in narcolepsy with cataplexy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The evolutionarily conserved miRNA-137 targets the neuropeptide hypocretin/orexin and modulates the wake to sleep ratio.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Chronic cerebral aspects of long COVID, post-stroke syndromes and similar states share their pathogenesis and perispinal etanercept treatment logic.Pharmacology research & perspectives · 2022Review
- Research Progress of Liujunzi Decoction in the Treatment of Tumor-Associated Anorexia.Drug design, development and therapy · 2022Review
- Background to new treatments for COVID-19, including its chronicity, through altering elements of the cytokine storm.Reviews in medical virology · 2021Review
- Article
- Cortical Transcriptomic Alterations in Association With Appetitive Neuropeptides and Body Mass Index in Posttraumatic Stress Disorder.The international journal of neuropsychopharmacology · 2021Article
- Article
- Pharmacological and chemogenetic orexin/hypocretin intervention ameliorates Hipp-dependent memory impairment in the A53T mice model of Parkinson's disease.Molecular brain · 2019Article
- Molecular mechanism of tumour necrosis factor alpha regulates hypocretin (orexin) expression, sleep and behaviour.Journal of cellular and molecular medicine · 2019Article
- Activation of orexinergic and histaminergic pathway involved in therapeutic effect of histamine HNaunyn-Schmiedeberg's archives of pharmacology · 2019Article
- Molecular Mechanisms of Cancer-Induced Sleep Disruption.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Recent studies recognize that Hypocretin system (also known as Orexin) plays a critical role in sleep/wake disorders and feeding behaviors. However, little is known about the regulation of the Hypocretin system. It is also known that tumor necrosis factor alpha (TNF-α) is involved in the regulation of sleep/wake cycle. Here, we test our hypothesis that the Hypocretin system is regulated by TNF-α. Prepro-Hypocretin and Hypocretin receptor 2 (HcrtR2) can be detected at a very low level in rat B35 neuroblastoma cells. In response to TNF-α, Prepro-Hypocretin mRNA and protein levels are down-regulated, and also HcrtR2 protein level is down-regulated in B35 cells. To investigate the mechanism, exogenous rat Prepro-Hypocretin and rat HcrtR2 were overexpressed in B35 cells. In response to TNF-α, protein and mRNA of Prepro-Hypocretin are significantly decreased (by 93% and 94%, respectively), and the half-life of Prepro-Hypocretin mRNA is decreased in a time- and dose-dependent manner. The level of HcrtR2 mRNA level is not affected by TNF-α treatment; however, HcrtR2 protein level is significantly decreased (by 86%) through ubiquitination in B35 cells treated with TNF-α. Downregulation of cellular inhibitor of apoptosis protein-1 and -2 (cIAP-1 and -2) abrogates the HcrtR2 ubiquitination induced by TNF-α. The control green fluorescent protein (GFP) expression is not affected by TNF-α treatment. These studies demonstrate that TNF-α can impair the function of the Hypocretin system by reducing the levels of both Prepro-Hypocretin and HcrtR2.
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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.