FK506 and the role of the immunophilin FKBP-52 in nerve regeneration

Drug Metab Rev. 1999 Aug;31(3):649-63. doi: 10.1081/dmr-100101940.

Abstract

In summary, FKBP-12 does not mediate the neurite outgrowth-promoting properties of neuroimmunophilin ligands (e.g., FK506). Instead, the neurotrophic properties of neuroimmunophilin ligands (FK506) and steroid hormones are mediated by disruption of steroid-receptor complexes. It remains unclear which component mediates neurite outgrowth, although the most likely candidates are FKBP-52, hsp-90, and p23 [42]. Regardless of the underlying mechanism involved, the FKBP-52 antibody data reveal that it should be possible to design, based on the structure of FK506, non-FKBP-12-binding (nonimmunosuppressant) compounds selective for FKBP-52 and test these new libraries for their ability to augment nerve regeneration. It may also be possible to exploit the structure of geldanamycin to develop a new class of hsp-90-binding compounds for use in nerve regeneration.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies / immunology
  • Benzoquinones
  • Humans
  • Immunophilins / immunology*
  • Immunosuppressive Agents / pharmacology
  • Lactams, Macrocyclic
  • Mice
  • Mice, Knockout
  • Molybdenum / pharmacology
  • Nerve Regeneration / immunology*
  • Neurites / drug effects
  • Neurites / physiology
  • Quinones / pharmacology
  • Steroids / pharmacology
  • Tacrolimus / pharmacology*
  • Tacrolimus Binding Proteins

Substances

  • Antibodies
  • Benzoquinones
  • Immunosuppressive Agents
  • Lactams, Macrocyclic
  • Quinones
  • Steroids
  • molybdate
  • Molybdenum
  • Tacrolimus Binding Proteins
  • Immunophilins
  • Tacrolimus
  • geldanamycin