机构：[a]Department of Veterinary Pathology, College of Animal Sciences, Henan Institute of Science and Technology, Xinxiang, China[b]State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street, Fengtai District, Beijing 100071, China[c]Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, 45Chang-Chun Street, Xicheng District, Beijing 100053, China神经外科首都医科大学宣武医院
Prion diseases are neurodegenerative disorders caused by the accumulation of misfolded prion proteins [scrapie form of PrPSc (PrPSc)]. PrPsc accumulation in the brain causes neurotoxicity by inducing mitochondrial-apoptotic pathways. Neurodegeneration can be prevented by imatinib mesylate (Gleevec or STI571) that regulates c-Abl tyrosine kinases, which elicit protective effects in neurodegenerative disease models. However, the protective effect of STI571 against prion disease remains unknown. In the present study, the effect of STI571 on prion peptide-induced neuronal death was investigated. Results showed that STI571 rescued neurons from PrP106-126-induced neurotoxicity by preventing mitochondria] dysfunction. STI571-inhibited c-Abl tyrosine kinases prevented PrP106-126-induced reduction in mitochondria] potential, Bax translocation to the mitochondria and cytochrome c release. The protective effect of STI571 against mitochondrial dysfunction was related to the activation of BIM expression. This study is the first to demonstrate the protective effect of STI571 against prion-mediated neurotoxicity. Our results suggested that imatinib mesylate treatment may be a novel therapeutic strategy to treat prion-mediated neurotoxicity. (C) 2015 Elsevier Ltd. All rights reserved.
基金：
the National Natural Science Foundation of China (Project No. 31372407),
Henan Scientific and technological project (Project No. 132102110118).
第一作者机构：[a]Department of Veterinary Pathology, College of Animal Sciences, Henan Institute of Science and Technology, Xinxiang, China
共同第一作者：
通讯作者：
通讯机构：[b]State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dong-Da Street, Fengtai District, Beijing 100071, China[*1]Department of Veterinary Pathology, College of Animal Sciences, Henan Institute of Science and Technology, Xinxiang 453003, China.
推荐引用方式(GB/T 7714)：
Yaoqian Pan,Liyong Sun,Jihong Wang,et al.STI571 protects neuronal cells from neurotoxic prion protein fragment-induced apoptosis[J].NEUROPHARMACOLOGY.2015,93:191-198.doi:10.1016/j.neuropharm.2015.01.029.
APA：
Yaoqian Pan,Liyong Sun,Jihong Wang,Wenzhuo Fu,Yongyao Fu...&Bo Pan.(2015).STI571 protects neuronal cells from neurotoxic prion protein fragment-induced apoptosis.NEUROPHARMACOLOGY,93,
MLA：
Yaoqian Pan,et al."STI571 protects neuronal cells from neurotoxic prion protein fragment-induced apoptosis".NEUROPHARMACOLOGY 93.(2015):191-198
