IMMUNOPHILINS MEDIATE THE NEUROPROTECTIVE EFFECTS OF FK506 IN FOCAL CEREBRAL-ISCHEMIA

被引:432
作者
SHARKEY, J
BUTCHER, SP
机构
[1] Fujisawa Institute of Neuroscience, Department of Pharmacology, University of Edinburgh
关键词
D O I
10.1038/371336a0
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
THE immunosuppressive action of the drug FK506 involves inhibition of calcineurin in T-lymphocytes by a complex of FK506 and an FK506 binding protein, FKBP 12(1,2), a member of the immunophilin protein family(3,4). The functional role of brain immunophilins is, however, unclear(5,6). We show here that FK506 is a powerful neuroprotective agent in an in vivo model of focal cerebral ischaemia when administered up to 60 min post-occlusion. The minimum effective neuroprotective dose is comparable with the immunosuppressant dose in humans(7), suggesting. that FK506 may have clinical potential for the treatment of stroke. Although the related immunosuppressants rapamycin and cyclosporin failed to reduce brain damage, the finding that rapamycin pretreatment blocked the effect of FK506 confirms a role for immunophilins in the neuroprotective mechanism.
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页码:336 / 339
页数:4
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