CNB-001, a pyrazole derivative of curcumin, has a variety of biological effects that may be beneficial for the treatment of neurodegenerative disorders including Alzheimer's disease. To further explore CNB-001 as a potential therapeutic drug, we investigated its effect on the morphology of astrocytes. Cultured rat cortical astrocytes exhibited flat, polygonal morphology in the absence of stimulation. When the cells were treated with CNB-001 (10 µM), they changed into process-bearing stellate cells. Since curcumin (10 µM) had no effect on astrocyte morphology, the stellation-inducing effect is likely to be specific for CNB-001. MTT reduction assay demonstrated that CNB-001 (10 µM) had no effect on the cell viability. The CNB-001-induced astrocyte stellation was inhibited by the presence of KN-93 (10 µM), an inhibitor of calcium/calmodulin-dependent protein kinase II (CaMKII), but not KN-92 (10 µM), an inactive analog of KN-93. These results suggest that CNB-001 induces astrocyte stellation through the activation of CaMKII.

To: 要旨(抄録)