ArticleCell death & disease2018
Toll-like receptor 4 modulation influences human neural stem cell proliferation and differentiation.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
23 citing papers in PubMed, 52 citations in OpenAlex.
- Validating Natural Compounds as Toll-Like Receptor 4 (TLR4) Antagonists: Experimental Challenges and Therapeutic Perspectives.Journal of medicinal chemistry · 2026Review
- A modified hot phenol-based protocol for high-purity Escherichia coli lipopolysaccharide extraction: Biochemical validation, stem cell cytotoxicity, and dose dependent multi-organ inflammation in a rat model.Biotechnology reports (Amsterdam, Netherlands) · 2025Article
- The Role of Prenatal Microglial Activation and Its Sex Differences in the Development of Neuropsychiatric Disorders and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Article
- Neonatal Exposure to Lipopolysaccharide Promotes Neurogenesis of Subventricular Zone Progenitors in the Developing Neocortex of Ferrets.International journal of molecular sciences · 2023Article
- Prenatal lipopolysaccharide exposure induces anxiety-like behaviour in male mouse offspring and aberrant glial differentiation of embryonic neural stem cells.Cellular & molecular biology letters · 2023Article
- Review
- TLR4 activation inhibits the proliferation and osteogenic differentiation of skeletal muscle stem cells by downregulating LGI1.Journal of physiology and biochemistry · 2022Article
- Toll-like receptors 2 and 4 differentially regulate the self-renewal and differentiation of spinal cord neural precursor cells.Stem cell research & therapy · 2022Article
- Article
- Gut-Brain Axis as a Pathological and Therapeutic Target for Neurodegenerative Disorders.International journal of molecular sciences · 2022Review
- Glial PAMPering and DAMPening of Adult Hippocampal Neurogenesis.Brain sciences · 2021Review
- TLR5 Supports Development of Placental Labyrinthine Zone in Mice.Frontiers in cell and developmental biology · 2021Article
- Strategies for Biomaterial-Based Spinal Cord Injury RepairFrontiers in bioengineering and biotechnology · 2021Review
- Toll-like receptor 4 differentially regulates adult hippocampal neurogenesis in an age- and sex-dependent manner.Hippocampus · 2020Article
- Diverse Roles for Hyaluronan and Hyaluronan Receptors in the Developing and Adult Nervous System.International journal of molecular sciences · 2020Review
- Neural Stem Cells from Shank3-ko Mouse Model Autism Spectrum Disorders.Molecular neurobiology · 2020Article
- Effect of chemical modulation of toll-like receptor 4 in an animal model of ulcerative colitis.European journal of clinical pharmacology · 2020Article
- GABAPsychopharmacology · 2019Review
- Effect of alternanRSC advances · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor 4 (TLR4) activation is pivotal to innate immunity and has been shown to regulate proliferation and differentiation of human neural stem cells (hNSCs) in vivo. Here we study the role of TLR4 in regulating hNSC derived from the human telencephalic-diencephalic area of the fetal brain and cultured in vitro as neurospheres in compliance with Good Manifacture Procedures (GMP) guidelines. Similar batches have been used in recent clinical trials in ALS patients. We found that TLR2 and 4 are expressed in hNSCs as well as CD14 and MD-2 co-receptors, and TLR4 expression is downregulated upon differentiation. Activation of TLR4 signaling by lipopolysaccharide (LPS) has a positive effect on proliferation and/or survival while the inverse is observed with TLR4 inhibition by a synthetic antagonist. TLR4 activation promotes neuronal and oligodendrocyte differentiation and/or survival while TLR4 inhibition leads to increased apoptosis. Consistently, endogenous expression of TLR4 is retained by hNSC surviving after transplantation in ALS rats or immunocompromised mice, thus irrespectively of the neuroinflammatory environment. The characterization of downstream signaling of TLR4 in hNSCs has suggested some activation of the inflammasome pathway. This study suggests TLR4 signaling as essential for hNSC self-renewal and as a novel target for the study of neurogenetic mechanisms.
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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.