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

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.