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PrPSc Inhibition and Cellular Protection of DBL on a Prion-Infected Cultured Cell via Multiple Pathways

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Abstract

Prion diseases are kinds of fatal neurodegenerative diseases without effective therapeutic and prophylactic tools currently. In this study, the inhibition of PrPSc propagation and cellular protectivity of 3,4-dihydroxybenzalacetone (DBL), a small catechol-containing compound isolated and purified from the ethanol extract of Inonotus obliquus, upon a prion-infected cell line SMB-S15 were evaluated. Western blots showed that after incubation with 10 μM of DBL for 14 days, the level of PrPSc in SMB-S15 cells was significantly decreased. Meanwhile, the levels of ROS and hydrogen peroxide were decreased with a dose-dependent manner, whereas the levels of some antioxidant factors, such as HO-1, GCLC and GCLM, were significantly increased. The activities of total glutathione and SOD were up-regulated. DBL-treated SMB-S15 cells also showed the up-regulation of UPR-related proteins, including PERK, IRE1α, ATF6 and GRP78, and activation of autophagy system. Furthermore, the SIRT3 abnormalities caused by prion infection were relieved by DBL treatment. On the contrary, these comprehensive changes were not significantly noticed in the normal partner cell line SMB-PS under the same experimental condition. Those data indicate that treatment of DBL on prion-infected cells can reduce PrPSc level, activate UPR and autophagy system and meanwhile relieve intracellular oxidative stress, endoplasmic reticulum stress and mitochondrial dysfunction by raising the levels of multiple antioxidant factors. The PrPSc inhibition and protective effectiveness of DBL upon the prion-infected cells in vitro make it worthy of further study.

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Data Availability

The datasets generated for this study are available on request to the corresponding authors.

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Acknowledgements

This paper was supported by National Natural Science Foundation of China (81772197, 81630062, 81401670), SKLID Development Grant (2021SKLID504, 2019SKLID401, 2019SKLID603).

Funding

This work was supported by National Natural Science Foundation of China (81772197, 81630062, 81401670), SKLID Development Grant (2021SKLID504, 2019SKLID401, 2019SKLID603).

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Author notes

  1. Wei Yang and Cao Chen contributed equally to this study

Authors and Affiliations

  1. State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China

    Wei Yang, Cao Chen, Jia Chen, Ying Xia, Chao Hu, Lin Wang, Yue-Zhang Wu, Qi Shi & Xiao-Ping Dong

  2. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, China

    Cao Chen, Qi Shi & Xiao-Ping Dong

  3. Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China

    Cao Chen & Xiao-Ping Dong

  4. College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing, China

    Lin Wang

  5. China Academy of Chinese Medical Sciences, Beijing, China

    Qi Shi & Xiao-Ping Dong

  6. Shenzhen Research Institute, Guangdong Ocean University, Shenzhen, China

    Zhi-Bao Chen

  7. College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang, China

    Zhi-Bao Chen

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Contributions

W.Y. and C.C. contributed to study design, performed assays and data analysis, and prepared the manuscript. J.C., Y.X. and Y.Z.W. assisted with the assays of Western Blot analysis. L.W. and C.H. assisted with the assays of cultured cells. Q.S. assisted with statistical analysis. C.C, Z.B.C. and X.P.D. corresponding authors, contributed to design, study concept and manuscript preparation.

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Correspondence to Cao Chen, Zhi-Bao Chen or Xiao-Ping Dong.

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Yang, W., Chen, C., Chen, J. et al. PrPSc Inhibition and Cellular Protection of DBL on a Prion-Infected Cultured Cell via Multiple Pathways. Mol Neurobiol 59, 3310–3321 (2022). https://doi.org/10.1007/s12035-022-02729-2

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