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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 547733
Title In Vitro Seeding Activity of Glycoform-Deficient Prions from Variably Protease-Sensitive Prionopathy and Familial CJD Associated with PrPV180I Mutation
Author(s) Wang, Zerui; Yuan, Jue; Shen, Pingping; Abskharon, Romany; Lang, Yue; Dang, Johnny; Adornato, Alise; Xu, Ling; Chen, Jiafeng; Feng, Jiachun; Moudjou, Mohammed; Kitamoto, Tetsuyuki; Langeveld, Jan; Appleby, Brian; Ma, Jiyan; Kong, Qingzhong; Petersen, Robert B.; Zou, Wen Quan; Cui, Li
Source Molecular Neurobiology 56 (2019)8. - ISSN 0893-7648 - p. 5456 - 5469.
DOI https://doi.org/10.1007/s12035-018-1459-0
Department(s) Infection Biology
Publication type Refereed Article in a scientific journal
Publication year 2019
Keyword(s) Humanized transgenic mice - Polymorphism - Prion - Prion disease - Real-time quaking-induced conversion (RT-QuIC) - Serial protein misfolding cyclic amplification (sPMCA) - Variably protease-sensitive prionopathy (VPSPr)
Abstract

Both sporadic variably protease-sensitive prionopathy (VPSPr) and familial Creutzfeldt-Jakob disease linked to the prion protein (PrP) V180I mutation (fCJDV180I) have been found to share a unique pathological prion protein (PrPSc) that lacks the protease-resistant PrPSc glycosylated at residue 181 because two of four PrP glycoforms are apparently not converted into the PrPSc from their cellular PrP (PrPC). To investigate the seeding activity of these unique PrPSc molecules, we conducted in vitro prion conversion experiments using serial protein misfolding cyclic amplification (sPMCA) and real-time quaking-induced conversion (RT-QuIC) assays with different PrPC substrates. We observed that the seeding of PrPSc from VPSPr or fCJDV180I in the sPMCA reaction containing normal human or humanized transgenic (Tg) mouse brain homogenates generated PrPSc molecules that unexpectedly exhibited a dominant diglycosylated PrP isoform along with PrP monoglycosylated at residue 181. The efficiency of PrPSc amplification was significantly higher in non-CJDMM than in non-CJDVV human brain homogenate, whereas it was higher in normal TgVV than in TgMM mouse brain homogenate. PrPC from the mixture of normal TgMM and Tg mouse brain expressing PrPV180I mutation (Tg180) but not TgV180I alone was converted into PrPSc by seeding with the VPSPr or fCJDV180I. The RT-QuIC seeding activity of PrPSc from VPSPr and fCJDV180I was significantly lower than that of sCJD. Our results suggest that the formation of glycoform-selective prions may be associated with an unidentified factor in the affected brain and the glycoform-deficiency of PrPSc does not affect the glycoforms of in vitro newly amplified PrPSc.

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