Butyrolactone derivative 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran-2(3H)-one protects against amyloid-β peptides-induced cytotoxicity in PC12 cells.

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 Aβ(25-35) 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 Aβ(25-35) 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 Aβ(25-35) and might be a promising tool for AD research.