Research Paper Volume 12, Issue 14 pp 14897—14917

Neuroprotective and neurogenic effects of novel tetramethylpyrazine derivative T-006 in Parkinson’s disease models through activating the MEF2-PGC1α and BDNF/CREB pathways

Figure 6. T-006 activates the MEF2/PGC1α/Nrf2 pathway through regulation of the Akt-GSK3β pathway. A53T and corrected DA neurons treated with T-006 and the positive drug at the indicated concentration for 24 hours. For MPP+-treatment assay, CGNs were pretreated with or without LY294002 (1 μM), Akt-iv (1 μM), or LiCl (10 μM) for 2 h, incubated with or without T-006 for 2 h, and finally exposed to MPP+. Cell viability was examined using an MTT assay. Luciferase reporter gene assays respectively included MEF2 (A), PGC1α (B), PGC1α-ΔMEF2 (C) and ARE (D). (E) Representative images of neurons co-stained with antibody against Nrf2 (green). DAPI (blue) indicates nucleus. (F) Luciferase reporter gene assays of MEF2 with MPP+ induction. (GK) respectively represent the fold changes of CDK5, MEF2D, PGC1α, Nrf1 and Nrf2 at mRNA level. (L) Effect of MEF2D reduction on MPP+-induced neurotoxicity in CGNs. (M) Effects of Akt pathway inhibitor LY294002 and GSK3β inhibitor on MEF2 transcriptional activity. (N) Effects of Akt pathway inhibitors LY294002 and Akt-iv, and GSK3β inhibitor on MPP+-induced neurotoxicity in CGNs. Data above are all from three independent experiments, expressed as mean±SEM. #P<0.05, ##P<0.01 and ###P<0.001 vs. control (Ctrl) group, and *P<0.05, **P<0.01, ***P<0.001 vs. MPP+ group.