Caffeine prevents human prion protein-mediated neurotoxicity through the induction of autophagy

Moon,Ji-Hong; Lee,Ju-Hee; Park,Jin-Young; Kim,Sung-Wook; Lee,You-Jin; Kang,Seog‑Jin; Seol,Jae-Won; Ahn,Dong-Choon; Park,Sang-Youel

doi:10.3892/ijmm.2014.1814

Caffeine prevents human prion protein-mediated neurotoxicity through the induction of autophagy

Authors:
- Ji-Hong Moon
- Ju-Hee Lee
- Jin-Young Park
- Sung-Wook Kim
- You-Jin Lee
- Seog‑Jin Kang
- Jae-Won Seol
- Dong-Choon Ahn
- Sang-Youel Park
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Affiliations: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea, National Institute of Animal Science, Rural Development Administration, Cheonan, Chungnam 330-801, Republic of Korea
Published online on: June 18, 2014 https://doi.org/10.3892/ijmm.2014.1814
Pages: 553-558

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Abstract

The human prion protein (PrP) fragment PrP(106‑126) possesses the majority of the pathogenic properties associated with the infectious scrapie isoform of PrP, known as PrPSc. The accumulation of PrPSc in the brain of humans and animals affects the central nervous system. Recent epidemiological studies have suggested that caffeine, one of the major components of coffee, exerts protective effects against the development of neurodegeneration. However, the protective effects of caffeine against prion disease have not been reported to date. In this study, we therefore investigated the effects of caffeine on PrP-mediated neurotoxicity. The protein expression of the autophagosomal marker, LC3-II, was increased by caffeine in a dose-dependent manner, and the autophagy induced by caffeine protected the neuronal cells against PrP(106‑126)‑induced cell death. On the contrary, the downregulation of LC3-II using the autophagy inhibitors, 3-methyladenine (3-ΜΑ) and wortmannin, prevented the caffeine-mediated neuroprotective effects. To the best of our knowledge, the present study provides the first evidence that treatment with caffeine protects human neuronal cells against prion‑mediated neurotoxicity and these neuroprotective effects are mediated by caffeine-induced autophagy signals. Our data suggest that treatment with caffeine may be a novel therapeutic strategy for prion peptide‑induced apoptosis.

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