title: Cellular cholesterol enrichment prevents prion peptide-induced neuron cell damages.
abstract: The prion diseases are neurodegenerative disorders characterized by the conversion of the PrPc (normal cellular prion) to the PrPsc (misfolded isoform). The accumulation of PrPsc within the central nervous system (CNS) leads to neurocytotoxicity by increasing oxidative stress. In addition, many neurodegenerative disorders including prion, Parkinson's and Alzheimer's diseases may be regulated by cholesterol homeostasis. The effects of cholesterol balance on prion protein-mediated neurotoxicity and ROS (reactive oxygen species) generation were the focus of this study. Cholesterol treatment inhibited PrP (106-126)-induced neuronal cell death and ROS generation in SH-SY5Y neuroblastoma cells. In addition, the PrP (106-126)-mediated increase of p53, p-p38, p-ERK and the decrease of Bcl-2 were blocked by cholesterol treatment. These results indicated that cellular cholesterol enrichment is a key regulator of PrP-106-126-mediated oxidative stress and neurotoxicity. Taken together, the results of this study suggest that modulation of cellular cholesterol appears to prevent the neuronal cell death caused by prion peptides.
authors.affiliation: Chonbuk National University, Center for Healthcare Technology Development, Bio-Safety Research Institute, College of Veterinary Medicine, Jeonju, Jeonbuk 561-756, South Korea.
authors.forename: Jae-Kyo
authors.initials: JK
authors.lastname: Jeong
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Seol
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Moon
authors.forename: Jae-Suk
authors.initials: JS
authors.lastname: Seo
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Jin-Shang
authors.initials: JS
authors.lastname: Kim
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D011328:Prions / Q000378:metabolism* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D011328:Prions; D017382:Reactive Oxygen Species; C082632:prion protein (106-126); D002784:Cholesterol