2008년 감베티 박사팀에 의해 보고된 프로티아제 효소에 의해 분해되는 프리온질병 (PSPr)
에 대한 후속연구가 [신경학연보(Annals of Neurology )] 2010년 8월호에 발표되었습니다.
2008년 보고에서는 129번 코돈의 VV형 유전자를 가진 11사례만 확인되었는데, 이번 연구
발표에서는 MV형 및 MM형 유전자를 가진 사람도 프로티아제 효소에 의해 분해되는
프리온질병에 감염된 사례를 보고하고 있습니다.
감베티 박사팀의 2008년 보고 이후 지난 2년간 30건 이상의 사례가 추가로 보고되었다고
합니다.
VV형 유전자와 MV형 유전자 사례의 차이는 Disease duration이 22개월~45개월로 차이가
났으며, 질병과 연관된 프리온 단백질의 protease digestion의 감수성이 차이가 나타났다고
합니다.
VV형 유전자는 protease digestion의 감수성이 높았으며, MV형 및 MM형 유전자는 감수성이
낮았다고 합니다.
그래서 연구진들은 “variably protease-sensitive prionopathy” (VPSPr)라는 용어를
만들어 냈다고 하며, VPSPr은 크로이츠펠트 야콥병(CJD)에 이어 두번째로 발견된
산발성 프리온 질병(sporadic prion protein disease)이 되었다고 합니다.
VPSPr becomes the second sporadic prion protein disease with this feature after Creutzfeldt-Jakob disease
Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein.
Wen-Quan Zou, Gianfranco Puoti, Xiangzhu Xiao, Jue Yuan, Liuting Qing, Ignazio Cali, Miyuki Shimoji, Jan P.M. Langeveld, Rudy Castellani, Silvio Notari, Barbara Crain, Robert E. Schmidt, Michael Geschwind, Stephen J. DeArmond, Nigel J. Cairns, Dennis Dickson, Lawrence Honig, Juan Maria Torres, James Mastrianni, Sabina Capellari, Giorgio Giaccone, Ermias D. Belay, Lawrence B. Schonberger, Mark Cohen, George Perry, Qingzhong Kong, Piero Parchi, Fabrizio Tagliavini and Pierluigi Gambetti.
출처 : Annals of Neurology Volume 68, Issue 2, pages 162–172, August 2010
http://onlinelibrary.wiley.com/doi/10.1002/ana.22094/abstract
Abstract
Objective:
The objective of the study is to report 2 new genotypic forms of protease-sensitive prionopathy (PSPr), a novel prion disease described in 2008, in 11 subjects all homozygous for valine at codon 129 of the prion protein (PrP) gene (129VV). The 2 new PSPr forms affect individuals who are either homozygous for methionine (129MM) or heterozygous for methionine/valine (129MV).
Methods:
Fifteen affected subjects with 129MM, 129MV, and 129VV underwent comparative evaluation at the National Prion Disease Pathology Surveillance Center for clinical, histopathologic, immunohistochemical, genotypical, and PrP characteristics.
Results:
Disease duration (between 22 and 45 months) was significantly different in the 129VV and 129MV subjects. Most other phenotypic features along with the PrP electrophoretic profile were similar but distinguishable in the 3 129 genotypes. A major difference laid in the sensitivity to protease digestion of the disease-associated PrP, which was high in 129VV but much lower, or altogether lacking, in 129MV and 129MM. This difference prompted the substitution of the original designation with “variably protease-sensitive prionopathy” (VPSPr). None of the subjects had mutations in the PrP gene coding region.
Interpretation:
Because all 3 129 genotypes are involved, and are associated with distinguishable phenotypes, VPSPr becomes the second sporadic prion protein disease with this feature after Creutzfeldt-Jakob disease, originally reported in 1920. However, the characteristics of the abnormal prion protein suggest that VPSPr is different from typical prion diseases, and perhaps more akin to subtypes of Gerstmann-Sträussler-Scheinker disease. ANN NEUROL 2010;68:162–172
