ArticleTranslational psychiatry2021
Neurosteroid allopregnanolone (3α,5α-THP) inhibits inflammatory signals induced by activated MyD88-dependent toll-like receptors.
Article in Translational psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
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The trial behind it
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Who cites it
55 citing papers in PubMed, 72 citations in OpenAlex.
- Associations of Allopregnanolone and Related Steroid Hormones with Prenatal Psychosocial Distress in the Healthy Start Cohort.medRxiv : the preprint server for health sciences · 2026Article
- Cholesterol metabolism in neurodegenerative diseases: mechanisms and therapeutic advances.Molecular neurodegeneration · 2026Review
- Structure-activity relationships of steroid and sterol neuromodulators on inflammatory markers in a murine microglial cell line.The Journal of steroid biochemistry and molecular biology · 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
- Brexanolone infusion produces sustained anti-inflammatory and neurotrophic effects in patients with postpartum depression that predict symptom improvement.Translational psychiatry · 2026Article
- Impact of impaired endogenous neurosteroidogenesis on outcomes following chronic alcohol exposure.bioRxiv : the preprint server for biology · 2026Article
- GABADrug design, development and therapy · 2026Review
- The role of neuroactive steroids in psychiatric and neurological disorders: Neurobiology and therapeutic perspectives.Neuroscience and biobehavioral reviews · 2025Review
- Gestational stress disrupts the neuroimmune environment in the nucleus accumbens of maternal rats.Brain, behavior, & immunity - health · 2025Article
- Serum steroid metabolome pattern is associated with the response to prednisolone therapy of male patients with IgA nephropathy.Renal failure · 2025Article
- Microglia alter sex-specific cerebellar myelination following placental hormone loss.Nature communications · 2025Article
- Neuroactive steroid exposure impacts neurodevelopment: Comparison of human and rodent placental contribution.Journal of neuroendocrinology · 2025Review
- New directions in neurosteroid therapeutics in neuropsychiatry.Neuroscience and biobehavioral reviews · 2025Review
- Neuroactive steroids and the pathophysiology of PTSD: Biomarkers for treatment targeting.Neuroscience and biobehavioral reviews · 2025Review
- Neuroactive steroids in the programming of neurodevelopment: implications of maternal obesity.Frontiers in endocrinology · 2025Review
- Is it possible to prevent excessive synaptic pruning in schizophrenia? Possibilities and limitations.Frontiers in synaptic neuroscience · 2025Review
- Structural modifications to pregnane neurosteroids alter inhibition of LPS/Lipid A binding at the MD-2 activation site within the TLR4 signaling complex.Frontiers in immunology · 2025Article
- Sertraline modulates hippocampal plasticity via sigma 1 receptors, cellular stress and neurosteroids.Translational psychiatry · 2024Article
- Novel Inhibitory Actions of Neuroactive Steroid [3α,5α]-3-Hydroxypregnan-20-One on Toll-like Receptor 4-Dependent Neuroimmune Signaling.Biomolecules · 2024Article
- Functional Food Nutrients, Redox Resilience Signaling and Neurosteroids for Brain Health.International journal of molecular sciences · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
We have shown that endogenous neurosteroids, including pregnenolone and 3α,5α-THP inhibit toll-like receptor 4 (TLR4) signal activation in mouse macrophages and the brain of alcohol-preferring (P) rat, which exhibits innate TLR4 signal activation. The current studies were designed to examine whether other activated TLR signals are similarly inhibited by 3α,5α-THP. We report that 3α,5α-THP inhibits selective agonist-mediated activation of TLR2 and TLR7, but not TLR3 signaling in the RAW246.7 macrophage cell line. The TLR4 and TLR7 signals are innately activated in the amygdala and NAc from P rat brains and inhibited by 3α,5α-THP. The TLR2 and TLR3 signals are not activated in P rat brain and they are not affected by 3α,5α-THP. Co-immunoprecipitation studies indicate that 3α,5α-THP inhibits the binding of MyD88 with TLR4 or TLR7 in P rat brain, but the levels of TLR4 co-precipitating with TRIF are not altered by 3α,5α-THP treatment. Collectively, the data indicate that 3α,5α-THP inhibits MyD88- but not TRIF-dependent TLR signal activation and the production of pro-inflammatory mediators through its ability to block TLR-MyD88 binding. These results have applicability to many conditions involving pro-inflammatory TLR activation of cytokines, chemokines, and interferons and support the use of 3α,5α-THP as a therapeutic for inflammatory disease.
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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.