4.7 Article

Melatonin-induced autophagy protects against human prion protein-mediated neurotoxicity

Journal

JOURNAL OF PINEAL RESEARCH
Volume 53, Issue 2, Pages 138-146

Publisher

WILEY
DOI: 10.1111/j.1600-079X.2012.00980.x

Keywords

autophagy; melatonin; mitochondrial dysfunction; neurotoxicity; prion disease

Funding

  1. Regional Research Universities Program
  2. Center for Healthcare Technology Development
  3. National Research Foundation of Korea
  4. Korean Government [2010-E00019]

Ask authors/readers for more resources

similar to Melatonin has neuroprotective effects in the models of neurodegenerative disease including Alzheimers and Parkinsons 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(106126)-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(106126)-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

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available