氧化应激
蛋白激酶R
莫里斯水上航行任务
超氧化物歧化酶
天麻素
药理学
化学
分子生物学
生物化学
生物
蛋白激酶A
激酶
内分泌学
海马体
丝裂原活化蛋白激酶激酶
色谱法
作者
Jingjing Zhang,Shufang Zhou,Q. Wang,Jiankuo Guo,Haoyang Liang,Jiao Deng,Wencan He
出处
期刊:Neuroscience
[Elsevier]
日期:2016-06-01
卷期号:325: 1-9
被引量:66
标识
DOI:10.1016/j.neuroscience.2016.03.024
摘要
The expression of β-site APP-cleaving enzyme 1 (BACE1) is increased in the brain of late-onset sporadic Alzheimer's disease (AD) and oxidative stress may be the potential cause of this event. The phenolic glucoside gastrodin (Gas), a main component of a Chinese herbal medicine Gastrodia elata Blume, has been demonstrated to display antioxidant activity and suppresses BACE1 expression. However, the mechanisms by which Gas suppresses BACE1 expression are not clear. Morris water maze test was performed to assess the effect of Gas treatment on memory impairments in Tg2576 mice. The level of oxidative stress in the brain of Tg2576 mice was determined by measuring the superoxide dismutase (SOD) activity, catalase (CAT) activity, and the levels of malondialdehyde (MDA) and ROS. In vivo and in vitro, we detected the expression levels of BACE1, pPKRThr446, PKR, pPERKThr981, PERK, peIF2αSer51, and eIF2α using western blot analysis. We found that Gas improved learning and memory abilities of Tg2576 transgenic mice and attenuated intracellular oxidative stress in hippocampi of Tg2576 mice. We discovered that the expression levels of BACE1, activated PKR (pPKRThr446) and activated eIF2α (peIF2αSer51) were elevated in the brains of Tg2576 mice and hydrogen peroxide (H2O2)-stimulated SH-SY5Y cells. Moreover, peptide PKR inhibitor (PRI) and Gas down-regulated BACE1 expression in Tg2576 mice and H2O2-stimulated SH-SY5Y cells by inhibiting activation of PKR and eIF2α. Gas alleviates memory deficits in mice and suppresses BACE1 expression by inhibiting the protein kinase/Eukaryotic initiation factor-2α (PKR/eIF2α) pathway. The research suggested that Gas may develop as an drug candidate in neurodegenerative diseases.
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