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

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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.