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Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein

BACKGROUND: Sporadic Creutzfeldt-Jakob disease is classified according to the genotype at polymorphic codon 129 (M or V) of the prion protein (PrP) gene and the type (1 or 2) of abnormal isoform of PrP (PrP(Sc)) in the brain. The most complicated entity in the current classification system is MV2, s...

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Autores principales: Kobayashi, Atsushi, Iwasaki, Yasushi, Otsuka, Hiroyuki, Yamada, Masahito, Yoshida, Mari, Matsuura, Yuichi, Mohri, Shirou, Kitamoto, Tetsuyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833290/
https://www.ncbi.nlm.nih.gov/pubmed/24252157
http://dx.doi.org/10.1186/2051-5960-1-74
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author Kobayashi, Atsushi
Iwasaki, Yasushi
Otsuka, Hiroyuki
Yamada, Masahito
Yoshida, Mari
Matsuura, Yuichi
Mohri, Shirou
Kitamoto, Tetsuyuki
author_facet Kobayashi, Atsushi
Iwasaki, Yasushi
Otsuka, Hiroyuki
Yamada, Masahito
Yoshida, Mari
Matsuura, Yuichi
Mohri, Shirou
Kitamoto, Tetsuyuki
author_sort Kobayashi, Atsushi
collection PubMed
description BACKGROUND: Sporadic Creutzfeldt-Jakob disease is classified according to the genotype at polymorphic codon 129 (M or V) of the prion protein (PrP) gene and the type (1 or 2) of abnormal isoform of PrP (PrP(Sc)) in the brain. The most complicated entity in the current classification system is MV2, since it shows wide phenotypic variations, i.e., MV2 cortical form (MV2C), MV2 with kuru plaques (MV2K), or a mixed form (MV2K + C). To resolve their complicated pathogenesis, we performed a comprehensive analysis of the three MV2 subgroups based on histopathological, molecular, and transmission properties. RESULTS: In histopathological and molecular analyses, MV2C showed close similarity to MM2 cortical form (MM2C) and could be easily discriminated from the other MV2 subgroups. By contrast, MV2K and MV2K + C showed the same molecular type and the same transmission type, and the sole difference between MV2K and MV2K + C was the presence of cortical pathology characteristic of MV2C/MM2C. The remarkable molecular feature of MV2K or MV2K + C was a mixture of type 2 PrP(Sc) and intermediate type PrP(Sc), which shows intermediate electrophoretic mobility between types 1 and 2 PrP(Sc). Modeling experiments using PrP-humanized mice indicated that MV2K contains a mixture of intermediate type PrP(Sc) with the 129M genotype (Mi PrP(Sc)) and type 2 PrP(Sc) with the 129V genotype (V2 PrP(Sc)) that originated from V2 PrP(Sc), whereas MV2C + K may also contain type 2 PrP(Sc) with the 129M genotype and cortical pathology (M2C PrP(Sc)) that lacks infectivity to the PrP-humanized mice in addition to Mi and V2 PrP(Sc). CONCLUSIONS: Taken together, the present study suggests that the phenotypic heterogeneity of MV2 stems from their different PrP(Sc) origin(s).
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spelling pubmed-38332902013-11-20 Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein Kobayashi, Atsushi Iwasaki, Yasushi Otsuka, Hiroyuki Yamada, Masahito Yoshida, Mari Matsuura, Yuichi Mohri, Shirou Kitamoto, Tetsuyuki Acta Neuropathol Commun Research BACKGROUND: Sporadic Creutzfeldt-Jakob disease is classified according to the genotype at polymorphic codon 129 (M or V) of the prion protein (PrP) gene and the type (1 or 2) of abnormal isoform of PrP (PrP(Sc)) in the brain. The most complicated entity in the current classification system is MV2, since it shows wide phenotypic variations, i.e., MV2 cortical form (MV2C), MV2 with kuru plaques (MV2K), or a mixed form (MV2K + C). To resolve their complicated pathogenesis, we performed a comprehensive analysis of the three MV2 subgroups based on histopathological, molecular, and transmission properties. RESULTS: In histopathological and molecular analyses, MV2C showed close similarity to MM2 cortical form (MM2C) and could be easily discriminated from the other MV2 subgroups. By contrast, MV2K and MV2K + C showed the same molecular type and the same transmission type, and the sole difference between MV2K and MV2K + C was the presence of cortical pathology characteristic of MV2C/MM2C. The remarkable molecular feature of MV2K or MV2K + C was a mixture of type 2 PrP(Sc) and intermediate type PrP(Sc), which shows intermediate electrophoretic mobility between types 1 and 2 PrP(Sc). Modeling experiments using PrP-humanized mice indicated that MV2K contains a mixture of intermediate type PrP(Sc) with the 129M genotype (Mi PrP(Sc)) and type 2 PrP(Sc) with the 129V genotype (V2 PrP(Sc)) that originated from V2 PrP(Sc), whereas MV2C + K may also contain type 2 PrP(Sc) with the 129M genotype and cortical pathology (M2C PrP(Sc)) that lacks infectivity to the PrP-humanized mice in addition to Mi and V2 PrP(Sc). CONCLUSIONS: Taken together, the present study suggests that the phenotypic heterogeneity of MV2 stems from their different PrP(Sc) origin(s). BioMed Central 2013-11-13 /pmc/articles/PMC3833290/ /pubmed/24252157 http://dx.doi.org/10.1186/2051-5960-1-74 Text en Copyright © 2013 Kobayashi et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kobayashi, Atsushi
Iwasaki, Yasushi
Otsuka, Hiroyuki
Yamada, Masahito
Yoshida, Mari
Matsuura, Yuichi
Mohri, Shirou
Kitamoto, Tetsuyuki
Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein
title Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein
title_full Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein
title_fullStr Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein
title_full_unstemmed Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein
title_short Deciphering the pathogenesis of sporadic Creutzfeldt-Jakob disease with codon 129 M/V and type 2 abnormal prion protein
title_sort deciphering the pathogenesis of sporadic creutzfeldt-jakob disease with codon 129 m/v and type 2 abnormal prion protein
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3833290/
https://www.ncbi.nlm.nih.gov/pubmed/24252157
http://dx.doi.org/10.1186/2051-5960-1-74
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