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The role of immunophilin ligands in nerve regeneration.

Abstract
Tacrolimus (FK506) is a widely used immunosuppressant in organ transplantation. However, it also has neurotrophic activity that occurs independently of its immunosuppressive effects. Other neurotrophic immunophilin ligands that do not exhibit immunosuppression have subsequently been developed and studied in various models of nerve injury. This article reviews the literature on the use of tacrolimus and other immunophilin ligands in peripheral nerve, cranial nerve and spinal cord injuries. The most convincing evidence of enhanced nerve regeneration is seen with systemic administration of tacrolimus in peripheral nerve injury, although clinical use is limited due to its immunosuppressive side effects. Local tacrolimus delivery to the site of nerve repair in peripheral and cranial nerve injury is less effective but requires further investigation. Tacrolimus can enhance outcomes in nerve allograft reconstruction and accelerates reinnervation of complex functional allograft transplants. Other non-immunosuppressive immunophilins ligands such as V-10367 and FK1706 demonstrate enhanced neuroregeneration in the peripheral nervous system and CNS. Mixed results are found in the application of immunophilin ligands to treat spinal cord injury. Immunophilin ligands have great potential in the treatment of nerve injury, but further preclinical studies are necessary to permit translation into clinical trials.
AuthorsEdward C Toll, Alexander M Seifalian, Martin A Birchall
JournalRegenerative medicine (Regen Med) Vol. 6 Issue 5 Pg. 635-52 (Sep 2011) ISSN: 1746-076X [Electronic] England
PMID21916598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Ligands
  • Nerve Growth Factors
  • Immunophilins
  • Tacrolimus
Topics
  • Animals
  • Immunophilins (chemistry, physiology)
  • Ligands
  • Nerve Growth Factors (chemistry, pharmacology)
  • Nerve Regeneration (drug effects, physiology)
  • Optic Nerve (physiology)
  • Peripheral Nerves (drug effects, physiology)
  • Spinal Cord (physiology)
  • Spinal Cord Injuries (pathology, therapy)
  • T-Lymphocytes (drug effects)
  • Tacrolimus (chemistry, pharmacology)

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