A synthetic peptide initiates Gerstmann-Straussler-Scheinker (GSS) disease in transgenic mice
A synthetic peptide initiates Gerstmann-Straussler-Scheinker (GSS) disease in transgenic mice
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DOI：
10.1006/jmbi.1999.3386
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发表时间：
2000-01-28
影响因子：
5.6
通讯作者：
Cohen, FE
中科院分区：
文献类型：
--
作者：
Kaneko, K;Ball, HL;Cohen, FE
朊病毒疾病的传染性、遗传性和散发性形式的分子基础最好用构象二态性蛋白来解释，该蛋白可以以不同的正常亚型和致病亚型存在。我们鉴定了一种突变型朊病毒蛋白的 55 个残基肽，它可以重折叠成至少两种不同的构象。当脑内接种到适当的转基因小鼠宿主中时，接受该肽β形式的20只小鼠中有20只在大约360天时出现中枢神经系统功能障碍的迹象，并出现格斯特曼-施特劳斯勒-沙恩克病的特征性神经组织学变化。相比之下，接受非 β 形式肽的 8 只小鼠中有 8 只在注射肽后 600 多天后没有出现任何神经病理学变化。我们的结论是，重新折叠成适当构象的化学合成肽可以加速或可能引发朊病毒疾病。 (C) 2000 年学术出版社。
The molecular basis of the infectious, inherited and sporadic forms of prion diseases is best explained by a conformationally dimorphic protein that can exist in distinct normal and disease-causing isoforms. We identified a 55-residue peptide of a mutant prion protein that can be refolded into at least two distinct conformations. When inoculated intracerebrally into the appropriate transgenic mouse host, 20 of 20 mice receiving the beta-form of this peptide developed signs of central nervous system dysfunction at similar to 360 days, with neurohistologic changes that are pathognomonic of Gerstmann-Straussler-Scheinker disease. By contrast, eight of eight mice receiving a non-beta-form of the peptide failed to develop any neuropathologic changes more than 600 days after the peptide injections. We conclude that a chemically synthesized peptide refolded into the appropriate conformation can accelerate or possibly initiate prion disease. (C) 2000 Academic Press.