Melatonin-mediated β-catenin activation protects neuron cells against prion protein-induced neurotoxicity

Activation of β‐catenin in neurons regulates mitochondrial function and protects against protein misfolding disorders, including Alzheimer's disease and Huntington's disease. Melatonin, a natural secretory product of the pineal gland, exerts neuroprotective effects through the activation o...

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Published in:Journal of pineal research 2014-11, Vol.57 (4), p.427-434
Main Authors: Jeong, Jae-Kyo, Lee, Ju-Hee, Moon, Ji-Hong, Lee, You-Jin, Park, Sang-Youel
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
beta Catenin - metabolism
Blotting, Western
Cell Line, Tumor
Humans
Immunohistochemistry
In Situ Nick-End Labeling
melatonin
Melatonin - pharmacology
Membrane Potential, Mitochondrial - drug effects
Neurons - metabolism
Neurons - pathology
Neuroprotective Agents - pharmacology
Peptide Fragments - toxicity
prion disease
Prions - toxicity
PrP 106-126
RNA, Small Interfering
Transfection
β-catenin
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Summary:Activation of β‐catenin in neurons regulates mitochondrial function and protects against protein misfolding disorders, including Alzheimer's disease and Huntington's disease. Melatonin, a natural secretory product of the pineal gland, exerts neuroprotective effects through the activation of β‐catenin. In this study, melatonin increased β‐catenin protein expression and activation in human neuroblastoma cell lines SH‐SY5Y cells. Melatonin also inhibited PrP (106–126)‐induced neurotoxicity and the inhibition attenuated by treatment of β‐catenin inhibitor ICG‐001. Activation of β‐catenin blocked PrP (106–126)‐mediated downregulation of anti‐apoptotic protein survivin and Bcl‐2. Reduction of mitochondrial membrane potential, translocation of Bax, and cytochrome c release which induced by PrP (106–126) treatment were inhibited by β‐catenin activation, which contributed to prevented PrP (106–126)‐induced neuronal cell death. In conclusion, β‐catenin activation by melatonin prevented PrP (106–126)‐induced neuronal cell death through regulating anti‐apoptotic proteins and mitochondrial pathways. These results also suggest the therapeutic value of Wnt/β‐catenin signaling in prion‐related disorders as influenced by melatonin.
ISSN:0742-3098
1600-079X
DOI:10.1111/jpi.12182