Oxidative Stress and Mitochondrial Dysfunction in Neurodegeneration of Transmissible Spongiform Encephalopathies (TSEs)
ABSTRACT Transmissible spongiform encephalopathies (TSEs) or prion diseases are neurodegenerative disorders that are invariably fatal in humans and animals. An important component of the infectious agent is a glyco-protein, termed PrPSc, which is derived from a normal cellular protein, termed PrPc. The pathogenic mechanisms of TSEs are not clear, but several factors such as oxidative stress and mitochondrial dysfunction have been reported to be involved. In the current review, we will present data that supports a role for oxidative stress and mitochondrial dysfunction in the induction of these diseases. We will discuss the pathways whereby oxidative stress and mitochondrial dysfunction could lead to neuronal damage and the clinical manifestations of TSE diseases.
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ABSTRACT: 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 down-regulation 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.This article is protected by copyright. All rights reserved.Journal of Pineal Research 09/2014; 57(4). DOI:10.1111/jpi.12182 · 7.81 Impact Factor