Immunosuppressant FK506 promotes neurite outgrowth in cultures of PC12 cells and sensory ganglia.

• DOI: 10.1073/pnas.91.8.3191
• Publication Date: 2006-05-31T13:08:01Z
• Authors: W E Lyons; E B George; T M Dawson; J P Steiner; S H Snyder
• Keywords: Neurite; FKBP; Hyperphosphorylation

The immunosuppressant drug FK506 acts by binding to receptor proteins, FK506-binding proteins (FKBPs), which in turn can bind and regulate a Ca(2+)-dependent phosphatase, calcineurin, Ca2+ release channel, the ryanodine receptor. Based on our findings regeneration models that levels of FKBPs during neural parallel those growth-associated protein GAP43, calcineurin substrate regulates neurite extension, we examined effects PC12 rat pheochromocytoma cells sensory ganglia. enhances outgrowth both systems increasing sensitivity nerve growth factor. Blockade actions ganglia rapamycin, an antagonist, establishes these involve FKBPs. Rapamycin itself stimulates cells. These are detected at subnanomolar concentrations, suggesting therapeutic application diseases involving degeneration.