Snyder S H, Sabatini D M, Lai M M, Steiner J P, Hamilton G S, Suzdak P D
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Trends Pharmacol Sci. 1998 Jan;19(1):21-6. doi: 10.1016/s0165-6147(97)01146-2.
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.
免疫亲和蛋白是环孢素A和FK506等免疫抑制剂药物的蛋白质受体，在大脑中的富集程度远高于免疫系统。药物 - 免疫亲和蛋白复合物与钙调神经磷酸酶结合，抑制其磷酸酶活性并产生免疫抑制作用。免疫亲和蛋白FKBP - 12（FK506结合蛋白，12 kDa）与兰尼碱和肌醇（1,4,5）三磷酸（IP3）受体形成复合物，以调节细胞内Ca2+的生理释放。在此，所罗门·斯奈德及其同事描述了非免疫抑制剂以及免疫抑制剂免疫亲和蛋白配体如何在培养系统和完整动物中对多种受损神经元具有神经营养作用。它们刺激受损坐骨神经、皮质胆碱能、多巴胺能和5 - HT神经元功能再生的能力可能具有治疗意义。
