Recombinant Human Prion Protein Inhibits Prion Propagation in vitro

被引：25

作者：

Yuan, Jue ^{[1
,3
]}

Zhan, Yi-An ^{[1
,7
]}

Abskharon, Romany ^{[5
,6
,17
]}

Xiao, Xiangzhu ^{[1
,3
]}

Martinez, Manuel Camacho ^{[1
,3
]}

Zhou, Xiaochen ^{[1
]}

Kneale, Geoff ^{[8
]}

Mikol, Jacqueline ^{[9
]}

Lehmann, Sylvain ^{[10
]}

Surewicz, Witold K. ^{[16
]}

Castilla, Joaquin ^{[12
,13
,14
,15
]}

Steyaert, Jan ^{[5
,6
]}

Zhang, Shulin ^{[1
]}

Kong, Qingzhong ^{[1
,2
,3
]}

Petersen, Robert B. ^{[1
,2
,11
]}

Wohlkonig, Alexandre ^{[5
,6
]}

Zou, Wen-Quan ^{[1
,2
,3
,4
,7
]}

机构：

[1] Case Western Reserve Univ, Sch Med, Dept Pathol, Cleveland, OH 44106 USA

[2] Case Western Reserve Univ, Sch Med, Dept Neurol, Cleveland, OH 44106 USA

[3] Case Western Reserve Univ, Sch Med, Natl Prion Dis Pathol Surveillance Ctr, Cleveland, OH 44106 USA

[4] Case Western Reserve Univ, Sch Med, Natl Ctr Regenerat Med, Cleveland, OH 44106 USA

[5] Vrije Univ Brussel, VIB, Dept Biol Struct, Brussels, Belgium

[6] Vrije Univ Brussel, Brussels, Belgium

[7] Nanchang Univ, Affiliated Hosp 1, Nanchang, Jiangxi, Peoples R China

[8] Univ Portsmouth, Inst Biomed & Biomol Sci, Biophys Lab, Portsmouth, Hants, England

[9] Paris Denis Diderot Univ, Hop Lariboisiere, Serv Anat & Cytol Pathol, Paris, France

[10] CHU Montpellier, IRB Hop ST ELOI, Montpellier, France

[11] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA

[12] Basque Fdn Sci, CIC bioGUNE, Derio 48160, Spain

[13] Basque Fdn Sci, IKERBASQUE, Derio 48160, Spain

[14] Basque Fdn Sci, CIC bioGUNE, Bilbao 48011, Spain

[15] Basque Fdn Sci, IKERBASQUE, Bilbao 48011, Spain

[16] Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA

[17] Natl Inst Oceanog & Fisheries NIFO, Cairo, Egypt

来源：

SCIENTIFIC REPORTS | 2013年 / 3卷

基金：

美国国家卫生研究院;

关键词：

CREUTZFELDT-JAKOB-DISEASE; SCRAPIE; PRP; CONVERSION; MICE; MODEL; SUSCEPTIBILITY; GLYCOSYLATION; ACCUMULATION; CONFORMERS;

D O I：

10.1038/srep02911

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页数：8

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