S14G-humanin restored cellular homeostasis disturbed by amyloid-beta protein
摘要
Humanin is a potential therapeutic agent for Alzheimer’s disease,and its derivative,S14G-humanin,is 1 000-fold stronger in its neuroprotective effect against Alzheimer’s disease-relevant insults.Although effective,the detailed molecular mechanism through which S14G-humanin exerts its effects remains unclear.Data from this study showed that fibrillar amyloid-beta 40 disturbed cellular homeostasis through the cell membrane,increasing intracellular calcium,generating reactive oxygen species,and decreasing the mitochondrial membrane potential.S14G-humanin restored these responses.The results suggested that S14G-humanin blocked the effects of amyloid-beta 40 on the neuronal cell membrane,and restored the disturbed cellular homeostasis,thereby exerting a neuroprotective effect on hippocampal neurons.