Selective inhibition of Tumor necrosis factor receptor-1 (TNFR1) for the treatment of autoimmune diseases |
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| Institution: | 1. Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, PR China;2. Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, HeNan Province, Zhengzhou 450001, Henan, PR China;3. Key Laboratory of Advanced Pharmaceutical Technology, Ministry of Education of China, HeNan Province, Zhengzhou 450001, Henan, PR China;1. Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;2. Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran;3. Department of Pathology, Shiraz Central Hospital, Shiraz, Iran;4. Breast Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;1. Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 39, Assam, India;2. Centre for Nanotechnology, Indian Institute of Technology Guwahati, Guwahati 39, Assam, India;1. Inflammation Research Center, VIB, Ghent, Belgium;2. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium;1. Kennedy Institute of Rheumatology, University of Oxford, OX3 7FY Oxford, UK;2. Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital-Keelung, Keelung, Taiwan;3. Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan;4. Department of Anatomic Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan;5. Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan;1. Experimental Medicine and Rheumtology, William Harvey Research Institute, Queen Mary University of London, London, UK;2. Kennedy Institute of Rheumatology, Oxford University, Oxford, UK;3. Department of Rheumatology, Royal Free Hospital, NHS Foundation Trust, London, UK;1. Department of Laboratory Medicine, The Affiliated People’s Hospital, Jiangsu University, Zhenjiang, China;2. Department of Immunology, Jiangsu Key Laboratory of Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang, China;3. Department of General Surgery, Affiliated Hospital of Jiangsu University, Jiefang Road No 438, Zhenjiang, Jiangsu, 212002, China |
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| 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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| Keywords: | TNF-α TNF receptors TNF inhibitors NF-κB Inflammation |
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