Immunosuppressive (FK506) and non-immunosuppressive (GPI1046) immunophilin ligands activate neurotrophic factors in the mouse brain.

Based on the fact that several recent reports have indicated that non-immunosuppressive immunophilin ligands (IPLs) can activate neurite outgrowth or nerve regeneration, we investigated the neurotrophic factor-activating abilities of IPLs in vivo in order to clarify the molecular basis of neurotrophic-like activity. Both FK506 (an immunosuppressive IPL) and GPI1046 (a non-immunosuppressive IPL) significantly increased glial cell line-derived neurotrophic factor (GDNF) content in the substantia nigra. In addition, FK506 increased striatal brain-derived neurotrophic factor (BDNF) content significantly. Thus, our present results suggest that the molecular basis of IPL-induced neurotrophic-like activity may be dependent on GDNF and/or BDNF activation.