Conclusions
Galantamine inhibits Aβ-induced cytostatic autophagy through decreasing ROS accumulation, providing new insights into deep understanding of AD progression and molecular basis of galantamine in neuroprotection.
Methods
Effects of galantamine on Aβ-induced cytotoxicity were checked by MTT, clone formation and apoptosis assays. The protein variations and reactive oxygen species (ROS) production were measured by western blotting analysis and dichloro-dihydro-fluorescein diacetate assay, respectively.
Results
Galantamine reversed Aβ-induced cell growth inhibition and apoptosis in neuron cells PC12. Aβ activated the entire autophagy flux and accumulation of autophagosomes, and the inhibition of autophagy decreased the protein level of cleaved-caspase-3 and Aβ-induced cytotoxicity. Meanwhile, galantamine suppressed Aβ-mediated autophagy flux and accumulation of autophagosomes. Moreover, Aβ upregulated ROS accumulation, while ROS scavengers N-acetyl-l-cysteine impaired Aβ-mediated autophagy. Further investigation showed that galantamine downregulated NOX4 expression to inhibit Aβ-mediated ROS accumulation and autophagy. Conclusions: Galantamine inhibits Aβ-induced cytostatic autophagy through decreasing ROS accumulation, providing new insights into deep understanding of AD progression and molecular basis of galantamine in neuroprotection.