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Inhibition of Autophagy by Captopril Attenuates Prion Peptide-Mediated Neuronal Apoptosis via AMPK Activation

  • Ji-Hong Moon
  • Jae-Kyo Jeong
  • Jeong-Min Hong
  • Jae-Won Seol
  • Sang-Youel Park
Article

Abstract

Accumulation of prion protein (PrPc) into a protease-resistant form (PrPsc) in the brains of humans and animals affects the central nervous system. PrPsc occurs only in mammals with transmissible prion diseases. Prion protein refers to either the infectious pathogen itself or the main component of the pathogen. Recent studies suggest that autophagy is one of the major functions that keep cells alive and which has a protective effect against neurodegeneration. In this study, we investigated whether the anti-hypertensive drug, captopril, could attenuate prion peptide PrP (106–126)-induced calcium alteration-mediated neurotoxicity. Treatment with captopril increased both LC3-II (microtubule-associated protein 1A/1B-light chain 3-II) and p62 protein levels, indicating autophagy flux inhibition. Electron microscopy confirmed the occurrence of autophagic flux inhibition in neuronal cells treated with captopril. Captopril attenuated PrP (106–126)-induced neuronal cell death via AMPK activation and autophagy inhibition. Compound C suppressed AMPK activation as well as the neuroprotective effects of captopril. Thus, these data showed that an anti-hypertensive drug has a protective effect against prion-mediated neuronal cell death via autophagy inhibition and AMPK activation, and also suggest that anti-hypertensive drugs may be effective therapeutic agents against neurodegenerative disorders, including prion diseases.

Keywords

Captopril Prion protein Autophagy flux Neurodegeneration AMPK 

Notes

Author Contributions

J.H.M., J.K.J., J.W.S., and S.Y.P. designed, executed the study, analyzed data, and wrote the manuscript. J.H.M. and J.K.J performed the electron microscopy. All authors have read and approved the final manuscript.

Funding Information

This study was supported by the National Research Foundation of the Korea Grant (MISP) funded by the Korean Government (2016R1A2B2009293).

Compliance with Ethical Standards

Ethical Approval

Ethical approval for the project was granted by the institutional review board of the Chonbuk National University.

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. 1.Biosafety Research Institute, College of Veterinary MedicineChonbuk National UniversityIksanSouth Korea

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