A Novel Neurotrophic Drug for Cognitive Enhancement and Alzheimer's Disease
Figure 2
Biological Activities of J147.
J147 is active with EC50 s between 10 and 200 nM in six different assays for neurotrophic activity and neurotoxicity. o-o, J147; x-x, CNB-001; Δ-Δ, curcumin. (A) Trophic Factor Withdrawal. Primary cortical neurons were prepared from 18-day-old rat embryos and cultured at low cell density with or without the three compounds. Cell viability was assayed 2 days later. (B) BDNF-like Activity. HT22 cells expressing the TrkB (BDNF) (open circles, J147) receptor or no TrkB (black circles, J147) were placed in serum-free medium in the presence of 50 ng/ml BDNF or the indicated amounts of compounds. Cell viability was determined 2 days later. Curcumin had no activity in this assay up to one micromolar. BDNF was used at 50 ng/ml and active only in cells expressing TrkB (open bar), not in its absence (black bar). (C) Oxidative Stress. E18 rat cortical neurons were treated with 5 mM glutamate and different concentrations of compounds one day after plating when no ionotropic glutamate receptors are expressed. Cell viability was measured 24 hr later. (D) Glucose Starvation. PC12 cells were starved for glucose plus or minus 20 nM J147, 0.2 µM CNB-001 or 10 µM curcumin and cell viability determined 48 hr later. J147 and NGF increase cell viability in the absence of glucose, *P<0.001 vs. control. CNB-001 and curcumin are inactive at 0.2 and 10 µM respectively (curcumin not shown). (E) Chemical ischemia. HT22 cells were treated with 20 µM iodoacetic acid for 2 hr alone or in the presence of varying concentrations of J147, CNB-001 or curcumin. Percent survival was measured after 24 hr. (F) Amyloid toxicity. Primary hippocampal cells were exposed to 5 µM Aβ1–42 in the presence of increasing amounts of compounds and cell viability determined 48 hr later. All data shown are mean ± SEM, n = 3 or 4. The curcumin and CNB-001 data which were included for comparison with J147 have been presented, in part, previously [8], [84].