Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is characterized by the extracellular deposition of β-amyloid (Aβ). Previous studies reported that resveratrol, a natural herbal compound isolated from grapes, could alleviate the development and progression of AD. However, the underlying mechanism is still unclear. In the study, amyloid beta-peptide1-42 (Aβ1-42) -treated the differentiated rat pheochromocytoma cell line (PC12) was chosen as an AD cellular model. Our data showed that resveratrol attenuated Aβ1-42-induced cell death and significantly enhanced mitophagy including an increase in acidic vesicular organelle number, LC3-II/LC3-I ratio, Parkin and Beclin-1 expression, and LC3 and TOMM20 co-localization in Aβ1-42-treated PC12 cells. However, 3-MA remarkably inhibited resveratrol-induced mitophagy. Resveratrol reduced apoptosis, decreased oxidative status and alleviated mitochondrial damage in Aβ1-42-treated PC12 cells. However, all of the protective effects were significantly blocked by 3-MA, suggesting that mitophagy was considerably involved in the neuroprotective effects of resveratrol via decreasing oxidative status. Our study suggests that mitophagy pathway may become a new targeted therapy to attenuate neuronal damage induced by AD.
Keywords: 3-MA; Apoptosis; Autophagy; Aβ1-42; Oxidative stress.
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