Recombinant Human Prion Protein Inhibits Prion Propagation in vitro

被引：0
作者：
Jue Yuan
Yi-An Zhan
Romany Abskharon
Xiangzhu Xiao
Manuel Camacho Martinez
Xiaochen Zhou
Geoff Kneale
Jacqueline Mikol
Sylvain Lehmann
Witold K. Surewicz
Joaquín Castilla
Jan Steyaert
Shulin Zhang
Qingzhong Kong
Robert B. Petersen
Alexandre Wohlkonig
Wen-Quan Zou
机构：
[1] Case Western Reserve University School of Medicine,Department of Pathology
[2] Case Western Reserve University School of Medicine,Department of Neurology
[3] National Prion Disease Pathology Surveillance Center,Department of Structural Biology
[4] Case Western Reserve University School of Medicine,Department of Neuroscience
[5] National Center for Regenerative Medicine,Department of Physiology and Biophysics
[6] Case Western Reserve University School of Medicine,undefined
[7] VIB,undefined
[8] Vrije Universiteit Brussels,undefined
[9] Structural Biology Brussels,undefined
[10] Vrije Universiteit Brussels,undefined
[11] The First Affiliated Hospital,undefined
[12] Nanchang University,undefined
[13] Biophysics Laboratories,undefined
[14] Institute of Biomedical and Biomolecular Sciences,undefined
[15] University of Portsmouth,undefined
[16] Hôpital Lariboisière,undefined
[17] Service d'Anatomie et Cytologie Pathologiques,undefined
[18] Paris Denis Diderot University,undefined
[19] IRB - Hôpital ST ELOI,undefined
[20] CHU de Montpellier,undefined
[21] Case Western Reserve University School of Medicine,undefined
[22] CIC bioGUNE and IKERBASQUE,undefined
[23] Basque Foundation for Science,undefined
[24] Case Western Reserve University School of Medicine,undefined
[25] National Institute of Oceanography and Fisheries (NIFO),undefined
来源：
Scientific Reports | / 3卷
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摘要：
Prion diseases are associated with the conformational conversion of the cellular prion protein (PrPC) into the pathological scrapie isoform (PrPSc) in the brain. Both the in vivo and in vitro conversion of PrPC into PrPSc is significantly inhibited by differences in amino acid sequence between the two molecules. Using protein misfolding cyclic amplification (PMCA), we now report that the recombinant full-length human PrP (rHuPrP23-231) (that is unglycosylated and lacks the glycophosphatidylinositol anchor) is a strong inhibitor of human prion propagation. Furthermore, rHuPrP23-231 also inhibits mouse prion propagation in a scrapie-infected mouse cell line. Notably, it binds to PrPSc, but not PrPC, suggesting that the inhibitory effect of recombinant PrP results from blocking the interaction of brain PrPC with PrPSc. Our findings suggest a new avenue for treating prion diseases, in which a patient's own unglycosylated and anchorless PrP is used to inhibit PrPSc propagation without inducing immune response side effects.
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