Autophagy induced by resveratrol prevents human prion protein-mediated neurotoxicity

► 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...

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Veröffentlicht in:Neuroscience research 2012-06, Vol.73 (2), p.99-105
Hauptverfasser: Jeong, Jae-Kyo, Moon, Myung-Hee, Bae, Bum-Chul, Lee, You-Jin, Seol, Jae-Won, Kang, Hyung-Sub, Kim, Jin-Shang, Kang, Seog-Jin, Park, Sang-Youel
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Sprache:eng
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Zusammenfassung:► 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. 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.
ISSN:0168-0102
1872-8111
DOI:10.1016/j.neures.2012.03.005