Abstract
The immunosuppressive oligonucleotide cyclosporine A (CsA) is extensively used in organ transplantation and autoimmune disorders. CsA as well as FK506 is a typical inhibitor of calcineurin, a serine/threonine phosphatase. Calcineurin is a potent regulator for fiber-type conversion, regeneration, and muscle hypertrophy of slow-twitch fibers. Many researchers including our group have used CsA delivered orally, intraperitoneally, or subcutaneously to modulate calcineurin activity. In this review, we have systematically and descriptively dealt with the role of CsA in regulating muscle adaptations in mature mammals. Pharmacological inhibition by CsA delays the muscle regenerating process. Some limitations are observed, because treatment with CsA in vivo blocks all of the calcineurin subtypes. A strategy for controlling the amount of calcineurin may be effective for the treatment of muscular disorders such as Duchenne muscular dystrophy (DMD), Ullrich congenital muscular dystrophy (UCMD), and limb-girdle muscular dystrophy (LGMD). Lowdose and short-term (2-6 weeks) CsA treatment would help to elucidate the functional role of calcineurin in skeletal muscle in vivo.
Keywords: Cyclosporine A, calcineurin, regeneration, hypertrophy, fiber type, muscular dystrophy, skeletal muscle, cyclophilin D, autoimmune disorders, calmodulin
Current Enzyme Inhibition
Title: Current Application of Cyclosporine A to Investigate Skeletal Muscle Adaptation
Volume: 7 Issue: 3
Author(s): Kunihiro Sakuma and Akihiko Yamaguchi
Affiliation:
Keywords: Cyclosporine A, calcineurin, regeneration, hypertrophy, fiber type, muscular dystrophy, skeletal muscle, cyclophilin D, autoimmune disorders, calmodulin
Abstract: The immunosuppressive oligonucleotide cyclosporine A (CsA) is extensively used in organ transplantation and autoimmune disorders. CsA as well as FK506 is a typical inhibitor of calcineurin, a serine/threonine phosphatase. Calcineurin is a potent regulator for fiber-type conversion, regeneration, and muscle hypertrophy of slow-twitch fibers. Many researchers including our group have used CsA delivered orally, intraperitoneally, or subcutaneously to modulate calcineurin activity. In this review, we have systematically and descriptively dealt with the role of CsA in regulating muscle adaptations in mature mammals. Pharmacological inhibition by CsA delays the muscle regenerating process. Some limitations are observed, because treatment with CsA in vivo blocks all of the calcineurin subtypes. A strategy for controlling the amount of calcineurin may be effective for the treatment of muscular disorders such as Duchenne muscular dystrophy (DMD), Ullrich congenital muscular dystrophy (UCMD), and limb-girdle muscular dystrophy (LGMD). Lowdose and short-term (2-6 weeks) CsA treatment would help to elucidate the functional role of calcineurin in skeletal muscle in vivo.
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Cite this article as:
Sakuma Kunihiro and Yamaguchi Akihiko, Current Application of Cyclosporine A to Investigate Skeletal Muscle Adaptation, Current Enzyme Inhibition 2011; 7 (3) . https://dx.doi.org/10.2174/157340811798807632
DOI https://dx.doi.org/10.2174/157340811798807632 |
Print ISSN 1573-4080 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6662 |
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