Autophagy induced by resveratrol prevents human prion protein-mediated neurotoxicity.

Neurosci Res

Korea Zoonoses Research Institute, Bio-Safety Research Institute, Center for Healthcare Technology Development, College of Veterinary Medicine, Chonbuk National University, Jeonju 561-756, South Korea.

Published: June 2012

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. Resveratrol 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.

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http://dx.doi.org/10.1016/j.neures.2012.03.005DOI Listing

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