S14G-humanin restored cellular homeostasis disturbed by amyloid-beta protein
Xue Li1, Wencong Zhao2, Hongqi Yang1
1Department of Neurology, Henan Provincial People's Hospital, Zhengzhou 450003, Henan Province, China ; Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China.
Abstract:
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. Al-though 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 ho-meostasis 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 neu-roprotective effect on hippocampal neurons.
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