青蒿琥酯
线粒体分裂
小胶质细胞
线粒体
神经退行性变
药理学
细胞生物学
淀粉样前体蛋白
生物
程序性细胞死亡
DNM1L型
阿尔茨海默病
细胞凋亡
医学
免疫学
炎症
病理
生物化学
疾病
恶性疟原虫
疟疾
作者
Yiren Qin,Chi‐Qian Ma,Jianhua Jiang,Dapeng Wang,Quan‐Quan Zhang,Mei‐Rong Liu,Hongru Zhao,Qi Fang,Yang Liu
摘要
Alzheimer's disease (AD) remains a leading cause of dementia and no therapy that reverses underlying neurodegeneration is available. Recent studies suggest the protective role of artemisinin, an antimalarial drug, in neurological disorders. In this study, we investigated the therapeutic potential of artesunate, a water-soluble derivative of artemisinin, on amyloid-beta (Aβ)-treated challenged microglial BV-2, neuronal N2a cells, and the amyloid precursor protein/presenilin (APP/PS1) mice model. We found that Aβ significantly induced multiple AD-related phenotypes, including increased expression/production of pro-inflammatory cytokines from microglial cells, enhanced cellular and mitochondrial production of reactive oxygen species, promoted mitochondrial fission, inhibited mitochondrial fusion, suppressed mitophagy or biogenesis in both cell types, stimulated apoptosis of neuronal cells, and microglia-induced killing of neurons. All these in vitro phenotypes were attenuated by artesunate. In addition, the over-expression of the mitochondrial fission protein Drp-1, or down-regulation of the mitochondrial fusion protein OPA-1 both reduced the therapeutic benefits of artesunate. Artesunate also alleviated AD phenotypes in APP/PS1 mice, reducing Aβ deposition, and reversing deficits in memory and learning. Artesunate protects neuronal and microglial cells from AD pathology, both in vitro and in vivo. Maintaining mitochondrial dynamics and simultaneously targeting multiple AD pathogenic mechanisms are associated with the protective effects of artesunate. Consequently, artesunate may become a promising therapeutic for AD.
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