Calcineurin, a well-conserved protein phosphatase 2B (PP2B), is a Ca2+-calmodulin-dependent serine/threonine protein phosphatase that is known to be involved in a myriad of cellular processes and signal transduction pathways. The biological role of calcineurin has been extensively studied in diverse groups of organisms. Homologues of mammalian and Drosophila calcineurin subunits exist in the nematode, Caenorhabditis elegans. The C. elegans counterpart of the catalytic subunit, calcineurin A, cna-1/tax-6, and the regulatory subunit, calcineurin B, cnb-1, are known to express ubiquitously in multiple tissues including neurons. The characterization of C. elegans calcineurin mutants facilitates identification of its physiological functions and signaling pathways. Genetic interactions between cna-1/tax-6 and cnb-1 mutants with a number of mutants involved in several signaling pathways have exemplified the pivotal role of calcineurin in regulating nematode development, behaviour and lifespan (aging). The present review has been aimed to provide a succinct summary of the multiple functions of calcineurin in C. elegans relating to its development, fertility, proliferation, behaviour and lifespan. Analyses of cna-1/tax-6 and cnb-1 interacting proteins and regulators of the phosphatase in this fascinating worm model have an immense scope to identify potential drug targets in various parasitic nematodes, which cause many diseases inflicting huge economic loss; and also for many human diseases, particularly neurodegenerative and myocardial diseases.
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http://dx.doi.org/10.1007/s12038-013-9319-6 | DOI Listing |
Clin Kidney J
January 2025
Division of Nephrology, School of Clinical Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong SAR.
Lupus nephritis is an important cause of severe glomerulonephritis, and a leading cause of kidney failure in young adults. While the disease can lead to rapid destruction of nephrons if untreated, there are effective therapies to reverse the severe acute kidney injury and prevent the lifetime risk of kidney failure. Early diagnosis and timely intervention are therefore of critical importance.
View Article and Find Full Text PDFIndian J Nephrol
July 2024
Department of Nephrology, Base Hospital, New Delhi, Delhi Cantt, India.
Obinutuzumab is a glycoengineered type II anti-CD20 monoclonal antibody with superior B cell cytotoxicity compared to rituximab. Various case reports suggest that in refractory phospholipase A2 receptor (PLA2R) positive membranous nephropathy (MN) patients, Obinutuzumab led to immunologic remission and improvement in proteinuria. In the present case series, we present six cases of difficult-to-treat PLA2R-associated MN refractory to prednisolone, calcineurin inhibitor (CNI), cyclophosphamide, and rituximab but subsequently responded to Obinutuzumab.
View Article and Find Full Text PDFNephrology (Carlton)
February 2025
Phoenix Children's Hospital-Thomas Campus, Phoenix, Arizona, USA.
Complement 3 glomerulonephritis (C3GN) is a rare glomerular disease involving dysregulation of the complement system. We describe our experience using pegcetacoplan, an inhibitor of C3 and its activation fragment, C3b, for treatment-resistant C3GN in a 9-year-old boy referred for evaluation of refractory membranoproliferative glomerulonephritis. Despite treatment with intense immunosuppression (high-dose steroids, mycophenolate mofetil and calcineurin inhibitor), he continued to have high disease activity with low C3 levels (35 mg/dL), hypertension, symptomatic oedema, anaemia, and nephrotic-range proteinuria (e.
View Article and Find Full Text PDFJAMA Pediatr
January 2025
Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Importance: Cyclophosphamide and calcineurin inhibitors are the most used nonsteroid immunosuppressive medications globally for children with various chronic inflammatory conditions. Their comparative effectiveness remains uncertain, leading to worldwide practice variation. Nephrotic syndrome is the most common kidney disease managed by pediatricians globally and suboptimal treatment is associated with high morbidity.
View Article and Find Full Text PDFClin Transplant
February 2025
Department of Transplant Nephrology, Transplant Surgery Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Calcineurin inhibitors have been the choice for maintenance immunosuppression (IS) in kidney transplant recipients (KTR), but they are associated with nephrotoxicity and metabolic side effects. We aim to compare the long-term outcomes of KTR on belatacept (bela) versus tacrolimus (tac) IS, in all KTRs and various subgroups. Using the UNOS-STAR files, we identified adult first-KTR from 2010 to 2022.
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