Autophagy induced by resveratrol prevents human prion protein-mediated neurotoxicity

Our previous study revealed that resveratrol blocks prion protein peptide PrP(106–126)-induced neurotoxicity. However, the mechanism of resveratrol-mediated neuroprotection in prion diseases is not clear. Resverstrol initiates neuroprotective effects via the activation of autophagy, which protects organelles, cells, and organisms against misfolded protein-disorders, including Alzheimer's disease and Parkinson's disease via regulation of mitochondrial homeostasis. Thus, we focused on elucidating the mechanisms responsible for resveratrol-mediated neuroprotection related to mitochondrial homeostasis as a result of autophagy activation. Resveratrol prevented PrP(106–126)-induced neuronal cell death by activating autophagy. Moreover, resveratrol-induced autophagy prevented the PrP(106–126)-induced reduction in mitochondrial potential and translocation of Bax to the mitochondria and cytochrome c release. Our results indicate that treatment with resveratrol appears to protect against neurotoxicity caused by prion protein peptides and the neuroprotection is induced by resveratrol-mediated autophagy signals.

► Resveratrol regulated mitochondrial homeostasis in neuronal cells.
► PrP(106–126)-induced mitochondrial dysfunction was blocked by resveratrol.
► Treatment of resveratrol increased LC3-II expression as an autophagy marker.
► Resveratrol-mediated autophagy blocked PrP(106–126)-induced mitochondrial damage.
► Activation of autophagy by resveratrol inhibits PrP(106–126)-mediated neurotoxicity.