期刊
AUTOPHAGY
卷 15, 期 10, 页码 1810-1828出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2019.1596476
关键词
Alborixin; alzheimer disease; amyloid beta; autophagy; microglial cells; primary neuronal cells
类别
资金
- Council of Scientific and Industrial Research, India [BSC-0205]
Imbalance in production and clearance of amyloid beta (A beta) is the primary reason for its deposition in Alzheimer disease. Macroautophagy/autophagy is one of the important mechanisms for clearance of both intracellular and extracellular A beta. Here, through screening, we identified alborixin, an ionophore, as a potent inducer of autophagy. We found that autophagy induced by alborixin substantially cleared A beta in microglia and primary neuronal cells. Induction of autophagy was accompanied by up regulation of autophagy proteins BECN1/Beclin 1, ATG5, ATG7 and increased lysosomal activities. Autophagy induced by alborixin was associated with inhibition of the phosphoinositide 3-kinase (PI3K)-AKT pathway. A knock down of PTEN and consistent, constitutive activation of AKT inhibited alborixin-induced autophagy and consequent clearance of A beta. Furthermore, clearance of A beta by alborixin led to significant reduction of A beta-mediated cytotoxicity in primary neurons and differentiated N2a cells. Thus, our findings put forward alborixin as a potential anti-Alzheimer therapeutic lead.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据