ArticleJournal of neurochemistry2013
Tuftsin signals through its receptor neuropilin-1 via the transforming growth factor beta pathway.
Article in Journal of neurochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
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- Neuropilins in Multiple Sclerosis: Dual Roles of NRP-1 in Neuroinflammation and Neuroprotection.Neuromolecular medicine · 2026Review
- Glioblastoma-associated macrophages in glioblastoma: from their function and mechanism to therapeutic advances.Cancer gene therapy · 2025Review
- Brain microenvironment orchestrates highly aggressive tumor variants: current trends and therapeutic approaches.Frontiers in aging neuroscience · 2025Review
- Nitric Oxide Therapeutics: New Hopes for More Effective Tuberculosis Treatment Combine with Targeted and Controlled Nanotechnology.International journal of nanomedicine · 2025Review
- Targeting CD44 and other pleiotropic co-receptors as a means for broad inhibition of tumor growth and metastasis.Clinical & experimental metastasis · 2024Review
- Functionalizing Dendrimers for Targeted Delivery of Bioactive Molecules to Macrophages: A Potential Treatment forPharmaceuticals (Basel, Switzerland) · 2023Review
- Suppressing Inflammation for the Treatment of Diabetic Retinopathy and Age-Related Macular Degeneration: Dazdotuftide as a Potential New Multitarget Therapeutic Candidate.Biomedicines · 2023Review
- The Oncogenesis of Glial Cells in Diffuse Gliomas and Clinical Opportunities.Neuroscience bulletin · 2023Review
- The Pathological Activation of Microglia Is Modulated by Sexually Dimorphic Pathways.International journal of molecular sciences · 2023Review
- From protein-protein interactions to immune modulation: Therapeutic prospects of targeting Neuropilin-1 in high-grade glioma.Frontiers in immunology · 2022Review
- Glial and myeloid heterogeneity in the brain tumour microenvironment.Nature reviews. Cancer · 2021Review
- Novel Compounds Targeting Neuropilin Receptor 1 with Potential To Interfere with SARS-CoV-2 Virus Entry.ACS chemical neuroscience · 2021Article
- In silico identification and validation of inhibitors of the interaction between neuropilin receptor 1 and SARS-CoV-2 Spike protein.bioRxiv : the preprint server for biology · 2020Article
- Discovery of a novel fluorescent chemical probe suitable for evaluation of neuropilin-1 binding of small molecules.Drug development research · 2020Article
- Tuftsin-Bearing Liposomes Co-Encapsulated with Doxorubicin and Curcumin Efficiently Inhibit EAC Tumor Growth in Mice.International journal of nanomedicine · 2020Article
- Treatment Effect of Tuftsin and Antigen Peptide Combined with Immune Cells on Colorectal Cancer.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Synchronous inhibition of mTOR and VEGF/NRP1 axis impedes tumor growth and metastasis in renal cancer.NPJ precision oncology · 2019Article
- Small Molecule Neuropilin-1 Antagonists Combine Antiangiogenic and Antitumor Activity with Immune Modulation through Reduction of Transforming Growth Factor Beta (TGFβ) Production in Regulatory T-Cells.Journal of medicinal chemistry · 2018Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Tuftsin (Thr-Lys-Pro-Arg) is a natural immunomodulating peptide found to stimulate phagocytosis in macrophages/microglia. Tuftsin binds to the receptor neuropilin-1 (Nrp1) on the surface of cells. Nrp1 is a single-pass transmembrane protein, but its intracellular C-terminal domain is too small to signal independently. Instead, it associates with a variety of coreceptors. Despite its long history, the pathway through which tuftsin signals has not been described. To investigate this question, we employed various inhibitors to Nrp1's coreceptors to determine which route is responsible for tuftsin signaling. We use the inhibitor EG00229, which prevents tuftsin binding to Nrp1 on the surface of microglia and reverses the anti-inflammatory M2 shift induced by tuftsin. Furthermore, we demonstrate that blockade of transforming growth factor beta (TGFβ) signaling via TβR1 disrupts the M2 shift similar to EG00229. We report that tuftsin promotes Smad3 phosphorylation and reduces Akt phosphorylation. Taken together, our data show that tuftsin signals through Nrp1 and the canonical TGFβ signaling pathway. Despite the 40-year history of the tetrapeptide tuftsin (TKPR), a macrophage and microglial activator, its mechanism of action has not been defined. Here, we report that the tuftsin-mediated anti-inflammatory M2 shift in microglia is caused specifically by tuftsin binding to the receptor neuropilin-1 (Nrp1) and signaling through TGFβ receptor-1, a coreceptor of Nrp1. We further show that tuftsin signals via the canonical TGFβ pathway and promotes TGFβ release from target cells.
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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.