Oncotarget

Research Papers: Gerotarget (Focus on Aging):

EGCG-mediated autophagy flux has a neuroprotection effect via a class III histone deacetylase in primary neuron cells

Ju-Hee Lee, Ji-Hong Moon, Sung-Wook Kim, Jae-Kyo Jeong, Uddin MD. Nazim, You-Jin Lee, Jae-Won Seol and Sang-Youel Park _

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Oncotarget. 2015; 6:9701-9717. https://doi.org/10.18632/oncotarget.3832

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Abstract

Ju-Hee Lee1,2, Ji-Hong Moon1,2, Sung-Wook Kim1,2, Jae-Kyo Jeong1,2, Uddin MD. Nazim1,2, You-Jin Lee1,2, Jae-Won Seol1 and Sang-Youel Park1,2

1 Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk, South Korea

2 Department of Bioactive Material Sciences and Research Center of Bioactive Materials, Chonbuk National University, Jeonju, Jeonbuk, South Korea

Correspondence to:

Jae-Won Seol, email:

Sang-Youel Park, email:

Keywords: EGCG, Sirt1, autophagy, prion, neurotoxicity

Received: February 10, 2015 Accepted: March 26, 2015 Published: April 14, 2015

Abstract

Prion diseases caused by aggregated misfolded prion protein (PrP) are transmissible neurodegenerative disorders that occur in both humans and animals. Epigallocatechin-3-gallate (EGCG) has preventive effects on prion disease; however, the mechanisms related to preventing prion diseases are unclear. We investigated whether EGCG, the main polyphenol in green tea, prevents neuron cell damage induced by the human prion protein. We also studied the neuroprotective mechanisms and proper signals mediated by EGCG. The results showed that EGCG protects the neuronal cells against human prion protein-induced damage through inhibiting Bax and cytochrome c translocation and autophagic pathways by increasing LC3-II and reducing and blocking p62 by using ATG5 small interfering (si) RNA and autophagy inhibitors. We further demonstrated that the neuroprotective effects of EGCG were exhibited by a class III histone deacetylase; sirt1 activation and the neuroprotective effects attenuated by sirt1 inactivation using sirt1 siRNA and sirtinol. We demonstrated that EGCG activated the autophagic pathways by inducing sirt1, and had protective effects against human prion protein-induced neuronal cell toxicity. These results suggest that EGCG may be a therapeutic agent for treatment of neurodegenerative disorders including prion diseases.


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