{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:10:53Z","timestamp":1776085853086,"version":"3.50.1"},"reference-count":56,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:00:00Z","timestamp":1619136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS109532"],"award-info":[{"award-number":["NS109532"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Prion is an infectious protein (PrPSc) that is derived from a cellular glycoprotein (PrPC) through a conformational transition and associated with a group of prion diseases in animals and humans. Characterization of proteinase K (PK)-resistant PrPSc by western blotting has been critical to diagnosis and understanding of prion diseases including Creutzfeldt-Jakob disease (CJD) and Gerstmann-Str\u00e4ussler-Scheinker (GSS) disease in humans. However, formation as well as biochemical and biological properties of the glycoform-selective PrPSc in variably protease-sensitive prionopathy (VPSPr) remain poorly understood. Here we reveal that formation of the ladder-like PrPSc in VPSPr is a PK-dependent two-step process, which is enhanced by basic pH. Two sets of PrPSc fragments can be identified with antibodies directed against an intermediate or a C-terminal domain of the protein. Moreover, antibodies directed against specific PrP glycoforms reveal faster electrophoretic migrations of PrP fragments mono-glycosylated at residue 181 and 197 in VPSPr than those in sporadic CJD (sCJD). Finally, RT-QuIC assay indicates that PrPSc-seeding activity is lower and its lag time is longer in VPSPr than in sCJD. Our results suggest that the glycoform-selective PrPSc in VPSPr is associated with altered glycosylation, resulting in different PK-truncation and aggregation seeding activity compared to PrPSc in sCJD.<\/jats:p>","DOI":"10.3390\/pathogens10050513","type":"journal-article","created":{"date-parts":[[2021,4,24]],"date-time":"2021-04-24T21:49:20Z","timestamp":1619300960000},"page":"513","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Further Characterization of Glycoform-Selective Prions of Variably Protease-Sensitive Prionopathy"],"prefix":"10.3390","volume":"10","author":[{"given":"Weiguanliu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Hospital of Jilin University, Changchun 130000, China"},{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangzhu","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingxuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Hospital of Jilin University, Changchun 130000, China"},{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jue","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron","family":"Foutz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6887-0190","authenticated-orcid":false,"given":"Mohammed","family":"Moudjou","sequence":"additional","affiliation":[{"name":"Molecular Virology and Immunology Unit (VIM), Universit\u00e9 Paris Saclay, INRAE, UVSQ, VIM, 78350 Jouy-en-Josas, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuyuki","family":"Kitamoto","sequence":"additional","affiliation":[{"name":"Department of Neurological Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Miyagi, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan P. M.","family":"Langeveld","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, Wageningen Bioveterinary Research, 8221RA 39 Lelystad, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Hospital of Jilin University, Changchun 130000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Quan","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"},{"name":"National Prion Disease Pathology Surveillance Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1073\/pnas.95.23.13363","article-title":"Prions","volume":"95","author":"Prusiner","year":"1998","journal-title":"Proc. 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