Affiliations: [a] Department of Neural Medicine, Second Hospital of Shandong University, Jinan, China | [b] Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan, China | [c] Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Science, Shandong University, Jinan, China
Correspondence:
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Correspondence to: JianZhong Bi, Department of Neural Medicine, Second Hospital of Shandong University, Jinan 250033, China. Tel.: +86 531 85875006; Fax: +86 531 88962544; E-mail: [email protected] and JunYing Miao, Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China. Tel.: +86 531 88364929; Fax: +86 531 88565610; E-mail: [email protected].
Abstract: Excessive extracellular deposition of amyloid-β peptides (Aβ) is a characteristic pathologic feature of Alzheimer's disease (AD). Accumulating evidence indicates that macroautophagy is involved in the pathogenesis of AD, but the exact role of macroautophapy is still unclear. We investigated whether Aβ25-35 could cause reactive oxygen species (ROS) accumulation, decrease the activity of Na+, K+-ATPase, trigger an autophagy process, and inhibit the growth of PC12 cells and examined the effect of a new autophagy modulator, butyrolactone derivative 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3 H)-one (3BDO). 3BDO could block the decrease in cell viability induced by Aβ25-35 by inhibiting ROS accumulation and the decrease in activity of Na+, K+-ATPase and the autophagy process. In addition, 3BDO modulated the autophagy progress via a mammalian target of rampamycin-dependent pathway. 3BDO has a protective effect against the cytotoxicity induced by Aβ25-35 and might be a promising tool for AD research.
