A STUDY OF REGENERATION OF DOPAMINE NEURONS MEDIATED BY IMMUNOPHILIN - A STUDY ON THE HUMAN AUTOPSIED BRAINS-

采用抗亲环蛋白（anti-CP）抗体免疫组化和免疫印迹法。对3例无神经系统疾病对照脑和4例帕金森脑的黑质（SN）和纹状体进行了检查。神经元抗cp抗体染色呈阳性。在1 / 3的对照和2 / 4的帕金森病患者中，18 kDa条带表示CP蛋白被识别。在正常和帕金森的大脑中证实了一种亲免疫蛋白的存在，这表明一种亲免疫蛋白配体可能用于治疗帕金森病。采用C57BL6小鼠MPTP模型研究了亲免疫素配体GPI 1046对神经元的神经保护作用。与GPI 1046处理组、对照组和GPI 1046 + mptp处理组相比，mptp处理组纹状体中DA含量显著降低（p < 0.01）。GPI 1046加mptp处理组与GPI 1046处理组或对照组DA含量无显著差异。本实验结果表明，GPI 1046可减轻MPTP对小鼠黑质神经元的毒性。期待非免疫抑制性亲免疫蛋白配体对帕金森病患者的神经保护治疗。

Immunohistochemical and immunoblotting methods were empibyed using anti-cyclophilin (anti-CP) antibody.The substantia nigra (SN) and the striatum from 3 control brains with no neurological diseases and 4 parkinsonian brains were examined. In parkinsonian SN, neurons were positively stained by anti-CP antibody. In one out of 3 controls and 2 out of 4 parkinsonians, 18 kDa band indicating CP protein was recognized. The presence of an immunophilin protein was demonstrated in normal and parkinsonian brains, indicating the possible therapeutic application of an immunophilin ligand for the therapy of Parkinson's diseape.The neuroprotective effect of an immunophilin ligand, GPI 1046, on the nigral neurons was examined using the C57BL6 mouse MPTP model. Compared to the GPI 1046-treated or vehicle control and GPI 1046 plus MPTP-treated groups, the DA content in the striatum of the MPTP-treated group was significantly low (p < O.O1). There was no significant djfference in the DA content between the GPI 1046 plus MPTP-treated group and the GPI 1046-treated or vehicle control groups. The present rcsults indicate that GPI 1046 attenuates MPTP toxicity to the nigrai neurons of mice.The neuroprotective therapy oh parkinsonian patients using non-imuunosuppressive immunophilin ligands is anticipated.