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Calcineurin
Calcineurin (CaN) is a calcium and calmodulin dependent serine/threonine protein phosphatase (also known as protein phosphatase 3, and calcium-dependent serine-threonine phosphatase). It activates the T cells of the immune system and can be blocked by drugs. Calcineurin activates nuclear factor of activated T cell cytoplasmic (NFATc), a transcription factor, by dephosphorylating it. The activated NFATc is then translocated into the nucleus, where it upregulates the expression of interleukin 2 (IL-2), which, in turn, stimulates the growth and differentiation of the T cell response. Calcineurin is the target of a class of drugs called calcineurin inhibitors, which include ciclosporin, voclosporin, pimecrolimus and tacrolimus. Structure Calcineurin is a heterodimer of a 61-kD calmodulin-binding catalytic subunit, calcineurin A and a 19-kD Ca2+-binding regulatory subunit, calcineurin B. There are three isozymes of the catalytic subunit, each encoded by a separate gene (PPP3CA, ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Immunosuppressive Drug
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified into five groups: * glucocorticoids * cytostatics * antibodies * drugs acting on immunophilins * other drugs Glucocorticoids In pharmacologic (supraphysiologic) doses, glucocorticoids, such as prednisone, dexamethasone, and hydrocortisone are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplantory immunosuppressants to prevent the acute transplant rejection and graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes. Immunosuppressive mechanism Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines Interleukin 1 (IL-1), IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ciclosporin
Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephrotic syndrome, and in organ transplants to prevent rejection. It is also used as eye drops for keratoconjunctivitis sicca (dry eyes). Common side effects include high blood pressure, headache, kidney problems, increased hair growth, and vomiting. Other severe side effects include an increased risk of infection, liver problems, and an increased risk of lymphoma. Blood levels of the medication should be checked to decrease the risk of side effects. Use during pregnancy may result in preterm birth; however, ciclosporin does not appear to cause birth defects. Ciclosporin is believed to work by decreasing the function of lymphocytes. It does this by forming a complex with cyclophilin to block the phosphatase activity of calcineurin, w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tacrolimus
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also be sold as a topical medication in the treatment of T-cell-mediated diseases such as eczema and psoriasis. For example, it is prescribed for severe refractory uveitis after a bone marrow transplant, exacerbations of minimal change disease, Kimura's disease, and vitiligo. It can be used to treat dry eye syndrome in cats and dogs. Tacrolimus inhibits calcineurin, which is involved in the production of interleukin-2, a molecule that promotes the development and proliferation of T cells, as part of the body's learned (or adaptive) immune response. Chemically, it is a macrolide lactone that was first discovered in 1987, from the fermentation broth of a Japanese soil sample that contained the bacterium ''Streptomyces tsukubensis''. It is on ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PPP3R1
Calcineurin subunit B type 1 also known as protein phosphatase 2B regulatory subunit 1 is a protein that in humans is encoded by the ''PPP3R1'' gene. Clinical significance The presence of a single nucleotide polymorphism rs1868402 in the ''PPP3R1'' gene is strongly correlated with rapid progress of Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me .... References Further reading * * * * * * * * * * * * * * * * * * {{protein-stub EF-hand-containing proteins ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PPP3CB
Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform (PP2BB) is an enzyme that in humans is encoded by the ''PPP3CB'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba .... References Further reading * * * * * * * * * * * * * * * * * * {{gene-10-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PPP3R2
Calcineurin subunit B type 2 is a protein that in humans is encoded by the ''PPP3R2'' gene. Among its related pathways are MAPK/ERK pathway, MAPK signaling pathway and GPCR pathway. GO annotations related to this gene include calcium ion binding. An important paralog of this gene is CHP1. References Further reading * * * * * * * * {{gene-9-stub EF-hand-containing proteins ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
T Cell Receptor
The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR. The TCR is composed of two different protein chains (that is, it is a heterodimer). In humans, in 95% of T cells the TCR consists of an alpha (α) chain and a beta (β) chain (encoded by '' TRA'' and ''TRB'', respectively), whereas in 5% of T cells the TCR consists of gamma and delta (γ/δ) chains (encoded by '' TRG'' and '' TRD'', respectively). This ratio changes during ontogeny and in diseased states (such as leukemia). It also differs between species. Orthologues of the 4 loci have been mapped in various species. Each locus can produce a vari ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
NFAT
Nuclear factor of activated T-cells (NFAT) is a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the development of cardiac, skeletal muscle, and nervous systems. NFAT was first discovered as an activator for the transcription of IL-2 in T cells (as a regulator of T cell immune response) but has since been found to play an important role in regulating many more body systems. NFAT transcription factors are involved in many normal body processes as well as in development of several diseases, such as inflammatory bowel diseases and several types of cancer. NFAT is also being investigated as a drug target for several different disorders. Family members The NFAT transcription factor family consists of five members NFATc1, NFATc2, NFATc3, NFATc4, and NFAT5. NFATc1 through NFATc4 are regulated by calcium signalling, and are known as the classical mem ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pimecrolimus
Pimecrolimus is an immunomodulating agent of the calcineurin inhibitor class used in the treatment of atopic dermatitis (eczema). It is available as a topical cream, once marketed by Novartis (however, Galderma has been promoting the compound in Canada since early 2007) under the trade name Elidel. Medical uses It has been proven to be effective in various inflammatory skin diseases, e.g., seborrheic dermatitis, cutaneous lupus erythematosus, oral lichen planus, vitiligo, and psoriasis. Tacrolimus and pimecrolimus are both calcineurin inhibitors and function as immunosuppressants. Side effects In January 2006, the United States Food and Drug Administration (FDA) announced that Elidel packaging would be required to carry a black box warning regarding the potential increased risk of lymph node or skin cancer, as for the similar drug tacrolimus, whereas current practice by UK dermatologists is not to consider this a significant real concern and they are increasingly recommend ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Voclosporin
Voclosporin, sold under the brand name Lupkynis, is a calcineurin inhibitor used as an immunosuppressant medication for the treatment of lupus nephritis. It is an analog of ciclosporin that has enhanced action against calcineurin and greater metabolic stability. It was approved for medical use in the United States in January 2021, and in the European Union in September 2022. Medical uses Lupus nephritis is a common form of glomerular nephritis occurring in patients with systemic lupus nephritis. Lupus nephritis commonly leads patients to chronic kidney failure and therefore places an emphasis on early intervention for improving treatment outcomes. Early intervention with voclosporin in combination with kidney response is believed to lead to more positive clinical outcomes for lupus nephritis patients. Thus, voclosporin is used in combination with background immunosuppressive regimen for the treatment of lupus nephritis. Safety has not been established in combination with cycl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
T Cell
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells, found in the bone marrow. Developing T cells then migrate to the thymus gland to develop (or mature). T cells derive their name from the thymus. After migration to the thymus, the precursor cells mature into several distinct types of T cells. T cell differentiation also continues after they have left the thymus. Groups of specific, differentiated T cell subtypes have a variety of important functions in controlling and shaping the immune response. One of these functions is immune-mediated cell death, and it is carried out by two major subtypes: CD8+ "killer" and CD4+ "helper" T cells. (These are named for the presence of the cell surface proteins CD8 or ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Serine/threonine Protein Phosphatase
The enzyme protein serine/threonine phosphatase (EC 3.1.3.16; systematic name protein-serine/threonine-phosphate phosphohydrolase) is a form of phosphoprotein phosphatase that acts upon phosphorylated serine/threonine residues: proteinserine/threonine phosphate + H2O = proteinserine/threonine + phosphate Serine and threonine phosphates are stable under physiological conditions, so a phosphatase enzyme has to remove the phosphate to reverse the regulation signal. Ser/Thr-specific protein phosphatases are regulated partly by their location within the cell and by specific inhibitor proteins. Serine and threonine are amino acids which have similar side-chain compositions that contain a hydroxyl group and thus can be phosphorylated by enzymes called serine/threonine protein kinases. The addition of the phosphate group can be reversed by enzymes called serine/threonine phosphatases. The addition and removal of phosphate groups regulates many cellular pathways involved in cell proli ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
