ArticleThe Journal of biological chemistry2019
The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 3 of them syntheses that pooled it.
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Who cites it
50 citing papers in PubMed, 3 syntheses or guidelines pooled it, 92 citations in OpenAlex.
- Efficacy and safety of anti-inflammatory drug-assisted treatment of symptoms in patients with schizophrenia: a meta-analysis.BMC psychiatry · 2026Pooled it
- Relationships Between Immune-Inflammatory Features and Social Cognitive Impairments in Patients With Schizophrenia Spectrum Disorders: A Systematic Review.Brain and behavior · 2025Pooled it
- An update on the efficacy of anti-inflammatory agents for patients with schizophrenia: a meta-analysis.Psychological medicine · 2019Pooled it
- Therapeutic potential of an ethnoveterinary formulation against Staphylococcus aureus-induced mastitis via modulating TLR-2/NOX-2 pathway.Journal of molecular histology · 2026Article
- Metabolic insights into the pathophysiology of tuberculous meningitis in FFPE postmortem human brain tissue.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Neurosteroid (3α,5α)3-hydroxypregnan-20-one enhancement of anti-inflammatory chemokine CX3CL1 exhibits sex, brain region, and cellular specificity in alcohol-preferring rats.Psychopharmacology · 2026Article
- Mechanistic insights into pregnenolone-mediated conidiation inhibition in Fusarium oxysporum.BMC microbiology · 2026Article
- Brexanolone infusion produces sustained anti-inflammatory and neurotrophic effects in patients with postpartum depression that predict symptom improvement.Translational psychiatry · 2026Article
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
- Serum steroid metabolome pattern is associated with the response to prednisolone therapy of male patients with IgA nephropathy.Renal failure · 2025Article
- A multiomics recovery factor predicts long COVID in the IMPACC study.The Journal of clinical investigation · 2025Article
- Neuroactive Steroids as Novel Promising Drugs in Therapy of Postpartum Depression-Focus on Zuranolone.International journal of molecular sciences · 2025Review
- The gut-microbiota-brain axis: Focus on gut steroids.Journal of neuroendocrinology · 2025Review
- Urine metabolomic analyses reveal metabolite disruptions in steroid hormone biosynthesis in monkeypox.iScience · 2025Article
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- Clinical Utility of Zuranolone for Postpartum Depression: A Narrative Review.Neuropsychiatric disease and treatment · 2025Review
- Hypothermic oxygenated perfusion inhibits CLIP1-mediated TIRAP ubiquitination via TFPI2 to reduce ischemia‒reperfusion injury of the fatty liver.Experimental & molecular medicine · 2024Article
- Protection from oxygen-glucose deprivation by neurosteroid treatment in primary neurons and oligodendrocytes.In vitro cellular & developmental biology. Animal · 2024Article
- Improvement in edema and cognitive recovery after moderate traumatic brain injury with the neurosteroid prodrug NTS-104.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Proteome-wide Mendelian randomization identified potential drug targets for migraine.The journal of headache and pain · 2024Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pregnenolone is a steroid hormone precursor that is synthesized in various steroidogenic tissues, in the brain, and in lymphocytes. In addition to serving as the precursor for other steroid hormones, pregnenolone exerts its own effect as an anti-inflammatory molecule to maintain immune homeostasis in various inflammatory conditions. Pregnenolone and its metabolic derivatives have been shown to have beneficial effects in the brain, including enhancing memory and learning, reversing depressive disorders, and modulating cognitive functions. A decreased level of pregnenolone has been observed in neuroinflammatory diseases, which emphasizes its role in neuroprotection and neuroregeneration. Although the anti-inflammatory property of pregnenolone was recognized several decades ago, its mechanism of action remains unknown. Here we report that pregnenolone promotes ubiquitination and degradation of the TLR2/4 adaptor protein TIRAP and TLR2 in macrophages and microglial cells. Pregnenolone and its metabolites suppressed the secretion of tumor necrosis factor α and interleukin-6 mediated through TLR2 and TLR4 signaling. Pregnenolone has been reported to induce activation of cytoplasmic linker protein 170, and this protein has recently been shown to promote targeted degradation of TIRAP. We observed enhanced degradation of TIRAP and TLR4 suppression by cytoplasmic linker protein 170 in the presence of pregnenolone. Our experimental data reveal novel nongenomic targets of pregnenolone and provide important leads to understand its role in restoring immune homeostasis in various inflammatory conditions.
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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.