title: Melatonin-induced autophagy protects against human prion protein-mediated neurotoxicity.
abstract: Melatonin has neuroprotective effects in the models of neurodegenerative disease including Alzheimer's and Parkinson's disease. Several studies have shown that melatonin prevents neurodegeneration by regulation of mitochondrial function. However, the protective action of melatonin has not been reported in prion disease. We investigated the influence of melatonin on prion-mediated neurotoxicity. Melatonin rescued neuronal cells from PrP(106-126)-induced neurotoxicity by prevention of mitochondrial dysfunction. Moreover, the protective effect of melatonin against mitochondrial dysfunction was related with autophagy activation. Melatonin-treated cells were dose-dependently increased in LC3-II, an autophagy marker. Melatonin-induced autophagy prevented a PrP(106-126)-induced reduction in mitochondrial potential and translocation of Bax to the mitochondria and cytochrome c release. On the other hand, downregulation of autophagy protein 5 with Atg5 siRNA or the autophagy blocker 3-methyladenine prevented the melatonin-mediated neuroprotective effects. This is the first report demonstrating that treatment with melatonin appears to protect against prion-mediated neurotoxicity and that the neuroprotection is induced by melatonin-mediated autophagy signals. The results of this study suggest that regulation of melatonin is a therapeutic strategy for prion peptide-induced apoptosis.
authors.affiliation: Korea Zoonoses Research Institute, Bio-Safety Research Institute, Center for Healthcare Technology Development, College of Veterinary Medicine, Chonbuk National University, Jeonju, Korea.
authors.forename: Jae-Kyo
authors.initials: JK
authors.lastname: Jeong
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Moon
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Seol
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
mesh_terms: D001343:Autophagy / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D006801:Humans; D020287:In Situ Nick-End Labeling; D008550:Melatonin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D011328:Prions / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference
chemical_list: D011328:Prions; D008550:Melatonin