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ACS Chem Neurosci. 2017 Nov 15;8(11):2535-2548. doi: 10.1021/acschemneuro.7b00273. Epub 2017 Aug 21.

Reduction of NF-κB (p65) in Scrapie-Infected Cultured Cells and in the Brains of Scrapie-Infected Rodents.

Ma Y1,2, Shi Q1,2, Wang J1,2, Xiao K1,2, Sun J1,2, Lv Y1,2, Guo M1,2, Zhou W1,2, Chen C1,2, Gao C1,2, Zhang BY1,2, Dong XP1,2,3.

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State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention , Chang-Bai Rd 155, Beijing 102206, People's Republic of China.
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University , Hangzhou, 310003, People's Republic of China.
Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences , Beijing 100101, People's Republic of China.


Transcription factor NF-κB functions as a pleiotropic regulator of target genes controlling physiological function as well as pathological processes of many different diseases, including some neurodegenerative diseases. However, the role of NF-κB in the pathogenesis of prion disease remains ambiguous. In this study, the status of NF-κB (p65) in a prion-infected cell line SMB-S15 was first evaluated. Significantly lower levels of p65 and the phosphorylated form of p65 (p-p65) were detected in SMB-S15 cells, compared with its normal partner cell line SMB-PS. Markedly slower responses of the NF-κB system to the stimulation of TNF-α were observed in SMB-S15 cells. Removal of PrPSc replication in SMB-S15 cells rescued the expression and activity of NF-κB. However, overexpression of p65 in SMB-S15 cells did not influence the propagation of PrPSc. Moreover, significant decline of p65 level was also observed in the brain tissues of mice infected with the lysates of SMB-S15 cells and hamsters infected with scrapie agent 263K at terminal stage. Immunofluorescence assays (IFAs) on brain sections from either normal or scrapie-infected rodents revealed colocalization of p65 with neuronal nuclear (NeuN) protein positive cells but not with glial fibrillary acidic protein (GFAP) positive cells. Assays of the agents involving in the regulation of NF-κB showed down-regulated phosphoinositide 3-kinase (PI3K) and protein kinase B (PKB/Akt) both in SMB-S15 cells and in the brains of scrapie-infected rodents. Those data indicate a remarkable repression of the classical NF-κB pathway during prion infection both in vitro and in vivo. The alteration of NF-κB (p65) shows close association with the replication and accumulation of PrPSc in the cells.


NF-κB (p65); Prion; TNF-α; phosphorylation; scrapie

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