NEURAL ACTIONS OF IMMUNOPHILIN LIGANDS

Immunophilins, protein receptors for immunosuppressant drugs such as c yclosporin A and FK506, are enriched far more in the brain than in the immune system. Drug-immunophilin complexes bind to calcineurin, inhib iting its phosphatase activity and leading to immunosuppressant effect s. The immunophilin FKBP-12 (FK506 binding protein, 12 kDa) forms a co mplex with the ryanodine and inositol (1,4,5) trisphosphate (IP3) rece ptors to regulate their physiological release of intracellular Ca2+. H ere, Solomon Snyder and colleagues describe how non-immunosuppressant as well as immunosuppressant immunophilin ligands are neurotrophic for numerous classes of damaged neurones, both in culture systems and int act animals. Their ability to stimulate functional regrowth of damaged sciatic, cortical cholinergic, dopamine and 5-HT neurones may have th erapeutic relevance.