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.
Gold
B G
BG
Department of Cell and Developmental Biology, Oregon Health Sciences University, Portland 97201, USA.
D000818:Animals; D000906:Antibodies / Q000276:immunology; D016227:Benzoquinones; D006801:Humans; D020104:Immunophilins / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D047029:Lactams, Macrocyclic; D051379:Mice; D018345:Mice, Knockout; D008982:Molybdenum / Q000494:pharmacology; D009416:Nerve Regeneration / Q000276:immunology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D011809:Quinones / Q000494:pharmacology; D013256:Steroids / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins
D000906:Antibodies; D016227:Benzoquinones; D007166:Immunosuppressive Agents; D047029:Lactams, Macrocyclic; D011809:Quinones; D013256:Steroids; C044659:molybdate; D008982:Molybdenum; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins; D016559:Tacrolimus; C001277:geldanamycin