Protective effect of benzothiazole derivative KHG21834 on amyloid β-induced neurotoxicity in PC12 cells and cortical and mesencephalic neurons

We have investigated the effect of KHG21834, a benzothiazole derivative, on the amyloid beta protein (A beta)-induced cell death in rat pheochromocytorna (PC 12) cells and rat cortical and mesencephalic neuron-glia cultures. KHG21834 attenuated the A beta(25-35) -induced apoptotic death in PC12 cells determined by characteristic morphological alterations and positive in situ terminal end-labeling (TUNEL). In the cortical neuron-glia cultures, KHG21834 reduced the A beta(25-35)-induced apoptosis determined by TUNEL staining. Immunocytochemical analysis and Western blot analysis of A beta(25-35)-induced neurotoxicity in mesencephalic neuron-glia cultures with anti-tyrosine hydroxylase (TH) antibody showed that A beta(25-35) decreased the expression of TH protein by 60% and KHG21834 significantly attenuated the A beta(25-35)-induced reduction in the expression of TH. Moreover, KHG21834 attenuates A beta(25-35)-induced toxicity concomitant with the reduction of activation of extracellular signal-regulated kinase (ERK)1/2 to a lesser extent. ERK1 was more sensitively affected than ERK2 in attenuation of A beta(25-35)-induced phosphorylation by KHG21834. These results demonstrated that KHG21834 was capable of protecting neuronal cells from A beta(25-35)-induced degeneration. (c) 2007 Elsevier Ireland Ltd. All rights reserved.