The immunosuppressant FK506 increases GAP-43 mRNA levels in axotomized sensory neurons

Immunophilin ligands in peripheral nerve regeneration

“…Presence of high levels of FKBP corresponds with the presence of high levels calcineurin [51,67]. The influence of FK506 on axon regeneration is predominantly through the binding to FKBP-12, which activates GAP-43 and the transforming growth factor (TGFb1) pathway [21,31]. The FK506--FKBP complex further binds to calcineurin, preventing the dephosphorylation of the nuclear factor of activated T cells and blocking the cascade of cytokine gene transcription.…”

“…A broad range of dosages (0.3-10 mg/kg) of the FK506 for peripheral nerve regeneration has been reported in the literature [4,20,22,30,31,39,46,52,77]. It can be thought that the wide range of these dosages may be due to the administration route of the FK506.…”

Intrinsic Factors Contributing to Axon Regeneration in the Mammalian Nervous System

“…To date, it is still unclear whether inosine may also promote regeneration of injured neurites. Improved regeneration, together with up-regulation of GAP-43, has been also obtained by administration of the immunosuppressant drug tacrolimus (FK-506), both in peripheral (Gold et al, 1995(Gold et al, , 1998 and in central neurons (Masden et al, 1998).…”

Effect of FK506 administration in alpha motor neurons after primary and delayed repair of the sciatic nerve

“…FK506 has been shown to exert neuroprotective effects in degenerative diseases, [30] ischemic insults, [31][32][33] spinal cord injury, [34,35] and neurite outgrowth in vitro. [36,37] Furthermore, treatment with FK506 has also been reported to enhance the rate of axonal regeneration in crush injury model [38][39][40][41] and in a peripheral nerve grafted into the injured spinal cord. [42] FK506 has been shown in many studies to enhance recovery after immediate [43] or delayed [29,38,44] nerve repair.…”