title: Caffeine prevents human prion protein-mediated neurotoxicity through the induction of autophagy.
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.
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Moon
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Jin-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Sung-Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: National Institute of Animal Science, Rural Development Administration, Cheonan, Chungnam 330-801, Republic of Korea.
authors.forename: Seog-Jin
authors.initials: SJ
authors.lastname: Kang
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Seol
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Dong-Choon
authors.initials: DC
authors.lastname: Ahn
authors.affiliation: Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D002110:Caffeine / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism; D011328:Prions / Q000037:antagonists & inhibitors / Q000378:metabolism; D012608:Scrapie / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D011328:Prions; C082632:prion protein (106-126); D002110:Caffeine