Selective inhibition of Tumor necrosis factor receptor-1 (TNFR1) for the treatment of autoimmune diseases
Abstract
Anti-TNF biologics have achieved great success in the treatment of autoimmune diseases and have been the most selling biologics on market. However, the anti-TNF biologics have shown some disadvantages such as poor efficacy to some patients and high risk of infection and malignancies during clinical application. Current anti-TNF biologics are antibodies or antibody fragments that bind to TNF-α and subsequently block both TNF-TNFR1 and TNF-TNFR2 signaling. Transgenic animal studies indicate that TNFR1 signaling is responsible for chronic inflammation and cell apoptosis whereas TNFR2 signaling regulates tissue regeneration and inflammation. Recent studies propose to selectively inhibit TNFR1 to enhance efficacy and avoid side effects. In this review, we introduce the biology of TNF-TNFR1 and TNF-TNFR2 signaling, the advantages of selective inhibition of TNF-TNFR1 signaling and research updates on the development of selective inhibitors for TNF-TNFR1 signaling. Antibodies, small molecules and aptamers that selectively inhibit TNFR1 have showed therapeutic potential and less side effects in preclinical studies. Development of selective inhibitors for TNFR1 is a good strategy to enhance the efficacy and reduce the side effects of anti-TNF inhibitors and will be a trend for next-generation of anti-TNF inhibitors.
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Transmembrane TNF and Its Receptors TNFR1 and TNFR2 in Mycobacterial Infections
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Osteoarthritis: molecular pathogenesis and potential therapeutic options
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Shang, H., Younas, A., & Zhang, N. (2022) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1778 · Cited by 40 · see citing works
Self-citationTNF-α-TNFR1 Signaling Mediates Inflammation and Bone Resorption in Apical Periodontitis.
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Recent advances in biomedical applications of smart nanomaterials: a comprehensive review
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TNF-α/TNFR1 activated astrocytes exacerbate depression-like behavior in CUMS mice
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Self-citationTNFα/TNFR1 signal induces excessive senescence of decidua stromal cells in recurrent pregnancy loss
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Application of aptamers in regenerative medicine
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Fighting fire with fire: The immune system might be key in our fight against Alzheimer’s disease
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Targeting Tumor Necrosis Factor Receptor 1 with Selected Aptamers for Anti-Inflammatory Activity
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DNA-based nanostructures for cell membrane receptor regulation and disease treatment
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Self-citationWang, H., Zhang, L., Sun, H., Xu, S., Li, K., & Su, X. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.124918 · Cited by 9 · see citing works
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Biogenic nanoparticles: Understanding their potential role in cancer theranostics
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Pollen‐Inspired Aptamer Delivery System for Multi‐Target Therapy in Rheumatoid Arthritis
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Review Article: TL1A Inhibitors in IBD ‐ Mechanistic Rationale and Clinical Evidence
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Nassr, N., Rharbaoui, F., Weitz, D., Gassenhuber, J., Rehberg, M., Kohlmann, M., Schumacher, F., Lahmar, A., Kovar, A., Perrin, L., et al. (2025) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3655 · Cited by 4 · see citing works
Peptide-Based Regulation of TNF-α-Mediated Cytotoxicity
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Recent Advancement in Drug Delivery Systems for the Treatment of Rheumatoid Arthritis
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Advantages of PROTACs in achieving selective degradation of homologous protein families
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Decoy peptides that inhibit TNF signaling by disrupting the TNF homotrimeric oligomer
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Zhao, M., Dai, J., Xu, H., Zhang, Y., & Wang, W. (2023) · Brain Behavior and Immunity Integrative · doi:10.1016/j.bbii.2023.100032 · Cited by 2 · see citing works
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Unlocking the potential of TNF: From biologic agents to small-molecule inhibitors
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Sidt2 Knockdown Aggravates Apical Periodontitis Via Autocrine Tumour Necrosis Factor-Alpha
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- Authors
- Zhang, N., Wang, Z., & Zhao, Y.
- Affiliations
- Zhengzhou University (CN)
- Corresponding author
- Zhao, Yongxing
- Venue
- Cytokine & Growth Factor Reviews
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 55
- Pages
- 80-85
- ISSN
- 1359-6101 (ISSN-L)
- OpenAlex
- W3015830230
- Cited by
- 72
- References
- 94
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 12 · 2023: 12 · 2022: 15 · 2021: 2 · 2020: 1
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cytokine & Growth Factor Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- tumor necrosis factor receptor 1, TNFR1 signaling, anti-TNF biologics, autoimmune disease, chronic inflammation, apoptosis, tissue regeneration, antibody fragments, small molecule inhibitors, aptamers
- MeSH terms
- Tumor Necrosis Factor Inhibitors, Animals, Autoimmune Diseases, Humans, Inflammation, Tumor Necrosis Factor-alpha, Receptors, Tumor Necrosis Factor, Type I, Receptors, Tumor Necrosis Factor, Type II
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