Agent-specific Shadoo responses in transmissible encephalopathies.
Agent-specific Shadoo responses in transmissible encephalopathies.
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DOI：
10.1007/s11481-010-9191-1
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发表时间：
2010-03
影响因子：
6.2
通讯作者：
Manuelidis, Laura
中科院分区：
文献类型：
--
作者：
Miyazawa, Kohtaro;Manuelidis, Laura
传染性海绵状脑病（TSE）是由具有病毒特性的感染因子引起的神经退行性疾病。宿主朊病毒蛋白（PrP）是晚期TSE病理学的标志物，与一种称为Shadoo（Sho）的类似蛋白质有关。Sho在感染RML羊瘙痒病因子的小鼠中减少，但尚未在其他TSE中进行研究。虽然PrP是TSE病原体感染所必需的，但尚不清楚Sho是否也需要。据推测，Sho保护细胞免受错误折叠的PrP的毒性作用。我们比较了Sho和PrP的变化后，感染非常不同的TSE代理，包括散发性CJD，亚洲CJD，新几内亚库鲁，vCJD（英国流行牛代理）和22 L羊瘙痒症，所有在标准小鼠传代。我们发现，Sho减少是代理特定的。标准小鼠中Sho变量的减少可以部分解释为区域神经病理学中的代理特异性差异。然而，Sho没有以任何定量或一致的方式跟踪PrP错误折叠。具有高鼠PrP水平的Tga 20小鼠显示了额外的试剂特异性差异。Sho不受亚洲克雅氏病的影响，但在Tga 20小鼠中库鲁剂显著降低;在标准小鼠中，两种药物均诱导相同的Sho降低。神经GT 1细胞的分析表明，Sho不是TSE感染所必需的。此外，由于所有感染的GT 1细胞看起来与未感染的对照组一样健康，因此不需要Sho来保护感染的细胞免受大量异常PrP和细胞内淀粉样蛋白的“毒性”负担。
Transmissible spongiform encephalopathies (TSE) are neurodegenerative diseases caused by an infectious agent with viral properties. Host prion protein (PrP), a marker of late stage TSE pathology, is linked to a similar protein called Shadoo (Sho). Sho is reduced in mice infected with the RML scrapie agent, but has not been investigated in other TSEs. Although PrP is required for infection by TSE agents, it is not known if Sho is similarly required. Presumably Sho protects cells from toxic effects of misfolded PrP. We compared Sho and PrP changes after infection by very distinct TSE agents including sporadic CJD, Asiatic CJD, New Guinea kuru, vCJD (the UK epidemic bovine agent) and 22L sheep scrapie, all passaged in standard mice. We found that Sho reductions were agent-specific. Variable Sho reductions in standard mice could be partly explained by agent-specific differences in regional neuropathology. However, Sho did not follow PrP misfolding in any quantitative or consistent way. Tga20 mice with high murine PrP levels revealed additional agent-specific differences. Sho was unaffected by Asiatic CJD yet was markedly reduced by the kuru agent in Tga20 mice; in standard mice both agents induced the same Sho reductions. Analyses of neural GT1 cells demonstrated that Sho was not essential for TSE infections. Furthermore, because all infected GT1 cells appeared as healthy as uninfected controls, Sho was not needed to protect infected cells from their “toxic” burden of abundant abnormal PrP and intracellular amyloid.
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影响因子：
2.5
作者：
Lloyd, Sarah E.;Grizenkova, Julia;Pota, Hirva;Collinge, John
通讯作者：
Collinge, John
DOI：
10.1073/pnas.0400158101
发表时间：
2004-06-08
影响因子：
11.1
作者：
Arjona, A;Simarro, L;Manuelidis, L
通讯作者：
Manuelidis, L
影响因子：
56.9
作者：
Manuelidis, L;Fritch, W;Xi, YG
通讯作者：
Xi, YG
影响因子：
3.7
作者：
Manuelidis, L;Fritch, W
通讯作者：
Fritch, W
影响因子：
56.9
作者：
Nishida, N;Katamine, S;Manuelidis, L
通讯作者：
Manuelidis, L