title: Autophagy induced by resveratrol prevents human prion protein-mediated neurotoxicity.
abstract: 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.
authors.affiliation: 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.
authors.forename: Jae-Kyo
authors.initials: JK
authors.lastname: Jeong
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Moon
authors.forename: Bum-Chul
authors.initials: BC
authors.lastname: Bae
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Seol
authors.forename: Hyung-Sub
authors.initials: HS
authors.lastname: Kang
authors.forename: Jin-Shang
authors.initials: JS
authors.lastname: Kim
authors.forename: Seog-Jin
authors.initials: SJ
authors.lastname: Kang
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
mesh_terms: D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011328:Prions / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011328:Prions; D013267:Stilbenes; C082632:prion protein (106-126); D000077185:Resveratrol