Discuss how Rheumatoid Arthritis results when the TNF-a pathway is inappropriately activated or not functioning properly .Expand on how the signaling pathway is disrupted in your answer. Int J Mol SciInt J Mol SciInt J Mol SciInt J Mol SciInt J Mol Sci. 2021 Mar; 22(5): 2719.Published online 2021 Mar 8. doi: 10.3390/ijms22052719The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and CurrentTNF-α Inhibitors in TherapeuticsDan-in Jang, 1,†A-Hyeon Lee,¹, Hye-Yoon Shin,2 Hyo-Ryeong Song,1,3 Jong-Hwi Park,1 Tae-Bong Kang,4Sang-Ryong Lee,5,* and Seung-Hoon Yang¹,*Arcangelo Liso, Academic Editor and Pio Conti, Academic Editor▸ Author information Article notes ▸ Copyright and License information DisclaimerAssociated Data▸ Data Availability StatementPMCID: PMC7962638PMID: 33800290AbstractGo to: ▸Tumor necrosis factor alpha (TNF-α) was initially recognized as a factor that causes the necrosis of tumors,but it has been recently identified to have additional important functions as a pathological component ofautoimmune diseases. TNF-α binds to two different receptors, which initiate signal transduction pathways.These pathways lead to various cellular responses, including cell survival, differentiation, and proliferation.However, the inappropriate or excessive activation of TNF-α signaling is associated with chronicinflammation and can eventually lead to the development of pathological complications such asautoimmune diseases. Understanding of the TNF-α signaling mechanism has been expanded and appliedfor the treatment of immune diseases, which has resulted in the development of effective therapeutic tools,including TNF-α inhibitors. Currently, clinically approved TNF-α inhibitors have shown noticeable potencyin a variety of autoimmune diseases, and novel TNF-α signaling inhibitors are being clinically evaluated. Inthis review, we briefly introduce the impact of TNF-α signaling on autoimmune diseases and its inhibitors,which are used as therapeutic agents against autoimmune diseases.1. IntroductionKeywords: TNF-α, autoimmune diseases, rheumatoid arthritis, inflammatory bowel disease, psoriaticarthritis, TNF-α inhibitorsGo to: ▸Tumor necrosis factor alpha (TNF-α) is a cytokine that has pleiotropic effects on various cell types. It hasbeen identified as a major regulator of inflammatory responses and is known to be involved in thepathogenesis of some inflammatory and autoimmune diseases [1]. Structurally, TNF-α is a homotrimerprotein consisting of 157 amino acids, mainly generated by activated macrophages, T-lymphocytes, andnatural killer cells [2]. It is functionally known to trigger a series of various inflammatory molecules,including other cytokines and chemokines. TNF-a exists in a soluble and transmembrane form. Thetransmembrane TNF-α (tmTNF-α) is the initially synthesized precursor form and is required to beprocessed by TNF-α-converting enzyme (TACE), a membrane-bound disintegrin metalloproteinase, to bereleased as the soluble TNF-α (STNF-α) [3]. The processed sTNF-α then facilitates various biologicalactivities through type 1 receptors (TNFR1, also known as TNFRSF1A, CD120a, and p55) and type 2receptors (TNFR2, also known as TNFRSF1B, CD120b, and p75) [4,5,6,7]. tmTNF-α also acts on bothTNFR1 and TNFR2, but its biological activities are expected to be mediated mainly through TNFR2 [8].TNFR1 is expressed by all human tissues and is the key signaling receptor for TNF-α. TNFR2 is generallyexpressed in immune cells and facilitates limited biological responses [2]. In general, TNF-α binds to itsreceptors, mainly TNFR1 and TNFR2, and then transmits molecular signals for biological functions such asinflammation and cell death. TNFR1 is activated by both sTNF-α and tmTNF-α, and it processes a deathdomain (DD) that interacts with the TNFR1-associated death domain (TRADD) adaptor protein [10].CFaveSHARERESOURSimilarCited ELinks t

Introduction:- The Rheumatoid arthritis is the chronic systemic of the autoimmune disease that…

J Mol Sci. 2021 Mar; 22(5): 2719. plished online 2021 Mar 8. doi: 10.3390/ijms22052719 e Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Curre F-α Inhibitors in Therapeutics -in Jang,¹,† A-Hyeon Lee,¹,† Hye-Yoon Shin,2 Hyo-Ryeong Song,1,3 Jong-Hwi Park,¹ Tae-Bong Kang,4 g-Ryong Lee,5,* and Seung-Hoon Yang¹,* angelo Liso, Academic Editor and Pio Conti, Academic Editor uthor information Article notes ▸ Copyright and License information ssociated Data Data Availability Statement stract PMCID: PMC79 PMID: 338 Disclaimer Introduction G mor necrosis factor alpha (TNF-α) was initially recognized as a factor that causes the necrosis of tu it has been recently identified to have additional important functions as a pathological component oimmune diseases. TNF-α binds to two different receptors, which initiate signal transduction pathw ese pathways lead to various cellular responses, including cell survival, differentiation, and prolifera wever, the inappropriate or excessive activation of TNF-α signaling is associated with chronic ammation and can eventually lead to the development of pathological complications such as oimmune diseases. Understanding of the TNF-a signaling mechanism has been expanded and appli the treatment of immune diseases, which has resulted in the development of effective therapeutic to luding TNF-α inhibitors. Currently, clinically approved TNF-α inhibitors have shown noticeable po a variety of autoimmune diseases, and novel TNF-α signaling inhibitors are being clinically evaluat review, we briefly introduce the impact of TNF-a signaling on autoimmune diseases and its inhibi ich are used as therapeutic agents against autoimmune diseases. ywords: TNF-α, autoimmune diseases, rheumatoid arthritis, inflammatory bowel disease, psoriatic ritis, TNF-α inhibitors Go nor necrosis factor alpha (TNF-α) is a cytokine that has pleiotropic effects on various cell types. It en identified as a major regulator of inflammatory responses and is known to be involved in the hogenesis of some inflammatory and autoimmune diseases [1]. Structurally, TNF-α is a homotrime tein consisting of 157 amino acids, mainly generated by activated macrophages, T-lymphocytes, an ural killer cells [2]. It is functionally known to trigger a series of various inflammatory molecules, luding other cytokines and chemokines. TNF-α exists in a soluble and transmembrane form. The ismembrane TNF-α (tmTNF-α) is the initially synthesized precursor form and is required to be cessed by TNF-α-converting enzyme (TACE), a membrane-bound disintegrin metalloproteinase, to eased as the soluble TNF-α (sTNF-α) [3]. The processed sTNF-a then facilitates various biological ivities through type 1 receptors (TNFR1, also known as TNFRSF1A, CD120a, and p55) and type 2 eptors (TNFR2, also known as TNFRSF1B, CD120b, and p75) [4,5,6,7]. tmTNF-α also acts on bot FR1 and TNFR2, but its biological activities are expected to be mediated mainly through TNFR2 [ FR1 is expressed by all human tissues and is the key signaling receptor for TNF-a. TNFR2 is gener ressed in immune cells and facilitates limited biological responses [2]. In general, TNF-α binds to intora maink TNER 1 and TNER? transmite maloouler signala for biological functio