The Proteasome Inhibitor Bortezomib Induces Neurogenesis and Toxicity in Rat Neural Stem Cells

Abstract

AbstractBackgroundDysregulation of protein degradation is related with various diseases including Alzheimer’s disease. Bortezomib is the first drug to treat multiple myeloma, however, the major side effect is induction of peripheral neuropathy. This study was performed to explore the effects and mechanisms of proteasome inhibition in neural stem cells (NSCs).MethodCortical neural stem cells were obtained and cultured from embryonic day 14 rats. By immunocytochemistry (ICC), western blot analysis and real‐time PCR followed by reverse transcription PCR, the cell fate of neural stem cells were identified. Toxicity was determined by MTT assay and neurosphere size measurement. BCL2‐BAX protein ratio was detected by western blot to explore the cytotoxic mechanisms.ResultNeurogenesis was significantly increased by bortezomib in proliferating NSCs when determine by ICC, western blot and PCR. However, such effect was not observed during NSC differentiation. In addition, Bortezomib induced toxicity in both proliferating NSCs and differentiated cells.ConclusionBortezomib is toxic to NSCs and differentiated cells, however, it induced neurogenesis in NSCs.