Department 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.
Department of Pharmacology, Zhengzhou Maternal and Child Health Hospital, Zhengzhou 450012, Henan Province, China.
Neural Regen Res. 2013 Sep 25;8(27):2573-80. doi: 10.3969/j.issn.1673-5374.2013.27.009.
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.
人源素是一种治疗阿尔茨海默病的潜在药物,其衍生物 S14G-人源素对阿尔茨海默病相关损伤的神经保护作用强 1000 倍。尽管有效,但 S14G-人源素发挥作用的详细分子机制仍不清楚。本研究数据显示,纤维状淀粉样β40 通过细胞膜扰乱细胞内稳态,增加细胞内钙,产生活性氧物质,并降低线粒体膜电位。S14G-人源素恢复了这些反应。结果表明,S14G-人源素阻止了淀粉样β40 对神经元细胞膜的作用,并恢复了紊乱的细胞内稳态,从而对海马神经元发挥了神经保护作用。