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| Nima Derakhshan* |
| Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran |
| *Corresponding author: |
Nima Derakhshan
Shiraz Nephro-Urology Research Center
Shiraz University of Medical Sciences
Shiraz, Iran, Pediatric office 71937
Namazi hospital, Shiraz, Iran
Tel: +98-9177161290
E-mail: Nima_med83@yahoo.com |
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| Received September 13, 2012; Published November 03, 2012 |
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| Citation: Derakhshan N (2012) Tacrolimus May Improve Neurologic Function in Solid Organ Transplant Recipients. 1:432. doi:10.4172/scientificreports.432 |
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| Copyright: © 2012 Derakhshan N. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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| Tacrolimus(FK506) is a macrolide immunosuppressant, introduced in 90’s and approved by FDA for prevention of allograft rejection in solid organ transplantations [1]. Tacrolimus and Cyclosporin A exert their immunosuppressive properties by binding to immunophillins. Immunophilins also called FK506 binding proteins (FKBPs) are prolyl-isomerases that participate in a wide variety of cellular functions including hormone signaling and protein folding [2]. Previous studies on Tacrolimus indicated broad functional roles for the immunophilins in the nervous system. |
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| Unlike Cyclosporine A, Tacrolimus readily crosses the brainblood- barrier and, thus together with its derivatives, may represent a novel approach to the treatment of neurological disorders [3]. |
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| Neuronal effect of Tacrolimus are explained via two different mechanisms; Neuroprotection via reduced NO formation (calcineurin-dependent mechanism) and a fast induction of heat shock proteins [3] and another process called neuroregeneration (via calcineurin-independent mechanisms).Thus, administration of non immunosuppressant ligands for FKBPs was hypothesized to represent important new drugs for the treatment of a variety of neurological disorders [1]. Animal study proved accelerated neuroregeneration after oral administration of a non immunosuppressant FKBP-12 ligand in rats [4]. |
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| The neuroregenerative property of Tacrolimus was believed to depend on the 12-kDa FK506-binding protein (FKBP-12). Another study suggested that the neuroregenerative properties of Tacrolimus and steroid hormones are mediated by disruption of steroid-receptor complexes. It remained unclear which component mediates neurite outgrowth, although the most likely candidates were FKBP-52, hsp-90, and p23 [5]. Gold BG et al. designed a study on human neuroblastoma SH-SY5Y cells, and proved that Immunophilin FKBP-52 (and not FKBP-12) mediates the neuroregenerative action of Tacrolimus. In these cells, the neuroregenerative action of Tacrolimus (10 pM to 10 nM) was completely prevented by the addition of a monoclonal antibody (50-100 nM) to the immunophilin FKBP-52 (also known as FKBP-59 or heat shock protein 56), a component of mature steroid receptor complexes [6]. |
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| This neuroregenerative aptitude of FK506 can be applied as a favorable pharmacologic potential, for selecting tacrolimus as the posttransplant immunosuppressant of choice for those who suffer from neurodegenerative disorders as well as end stage organ failure. |
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| Further studies, especially double-blind, placebo-controlled clinical trials on human allograft recipients who suffer a neurodegenerative disorder should be designed to study the neuronal effects of tacrolimus on human subjects. |
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| References |
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- Gold BG (1997)
- Sanokawa-Akakura R, Cao W, Allan K, Patel K, Ganesh A, et al. (2010)
- Klettner A, Herdegen T (2003)
- Gold BG, Zeleny-Pooley M, Chaturvedi P, Wang MS (1998)
- Gold BG (1999)
- Gold BG, Densmore V, Shou W, Matzuk MM, Gordon HS (1999)
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