Neural actions of immunophilin ligands.
Immunophilins, protein receptors for immunosuppressant drugs such as cyclosporin A and FK506, are enriched far more in the brain than in the immune system. Drug-immunophilin complexes bind to calcineurin, inhibiting its phosphatase activity and leading to immunosuppressant effects. The immunophilin FKBP-12 (FK506 binding protein, 12 kDa) forms a complex with the ryanodine and inositol (1,4,5) trisphosphate (IP3) receptors to regulate their physiological release of intracellular Ca2+. Here, 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 intact animals. Their ability to stimulate functional regrowth of damaged sciatic, cortical cholinergic, dopamine and 5-HT neurones may have therapeutic relevance.
Snyder
S H
SH
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sabatini
D M
DM
Lai
M M
MM
Steiner
J P
JP
Hamilton
G S
GS
Suzdak
P D
PD
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D016572:Cyclosporine / Q000187:drug effects* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008024:Ligands; D009420:Nervous System / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D016559:Tacrolimus / Q000378:metabolism / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006360:Heat-Shock Proteins; D008024:Ligands; D018377:Neurotransmitter Agents; D009569:Nitric Oxide; D016572:Cyclosporine; D022021:Tacrolimus Binding Proteins; D002118:Calcium; D016559:Tacrolimus