Is there a risk of prion-like disease transmission by Alzheimer- or Parkinson-associated protein particles?
Is there a risk of prion-like disease transmission by Alzheimer- or Parkinson-associated protein particles?
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DOI：
10.1007/s00401-014-1324-9
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发表时间：
2014-10
影响因子：
12.7
通讯作者：
Burger R
中科院分区：
文献类型：
--
作者：
Beekes M;Thomzig A;Schulz-Schaeffer WJ;Burger R
中枢神经系统中内源性蛋白质的错误折叠和聚集是阿尔茨海默病（AD）、帕金森病（PD）以及朊病毒疾病的神经病理学标志。被称为“成核依赖性聚集”的分子机制被认为是这种神经病理学现象的基础。根据这一概念，疾病相关蛋白质颗粒充当细胞核或种子，其募集细胞蛋白质并将它们以错误折叠的形式并入其生长的聚集结构中。实验研究表明，在实验室动物模型中，通过脑内（i.c.）注射含有各自蛋白质的聚集物质的接种物。这就提出了一个问题，即AD或PD是否可以像某些人类朊病毒疾病一样，通过可能存在于医疗器械或血液或血液制品中的自繁殖蛋白质颗粒在个体之间传播。虽然I.C.发现注射含有AD-或PD-相关蛋白聚集体的接种物引起神经元损伤和临床异常（例如，运动障碍）在一些动物模型中，迄今为止发表的研究都没有提供严重甚至致命疾病传播的证据。此外，现有的流行病学数据未表明AD或PD在人类之间的传播性。迄今为止发表的关于实验性传播的AD或PD相关蛋白种子的影响的研究结果并没有建议在血液疗法的背景下采取具体的预防措施，但需要在输血医学和其他医学领域保持警惕。
The misfolding and aggregation of endogenous proteins in the central nervous system is a neuropathological hallmark of Alzheimer’s disease (AD), Parkinson’s disease (PD), as well as prion diseases. A molecular mechanism referred to as “nucleation-dependent aggregation” is thought to underlie this neuropathological phenomenon. According to this concept, disease-associated protein particles act as nuclei, or seeds, that recruit cellular proteins and incorporate them, in a misfolded form, into their growing aggregate structure. Experimental studies have shown that the aggregation of the AD-associated proteins amyloid-β (Aβ) and tau, and of the PD-associated protein α-synuclein, can be stimulated in laboratory animal models by intracerebral (i.c.) injection of inocula containing aggregated species of the respective proteins. This has raised the question of whether AD or PD can be transmitted, like certain human prion diseases, between individuals by self-propagating protein particles potentially present on medical instruments or in blood or blood products. While the i.c. injection of inocula containing AD- or PD-associated protein aggregates was found to cause neuronal damage and clinical abnormalities (e.g., motor impairments) in some animal models, none of the studies published so far provided evidence for a transmission of severe or even fatal disease. In addition, available epidemiological data do not indicate a transmissibility of AD or PD between humans. The findings published so far on the effects of experimentally transmitted AD- or PD-associated protein seeds do not suggest specific precautionary measures in the context of hemotherapy, but call for vigilance in transfusion medicine and other medical areas.
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影响因子：
16.2
作者：
Giasson, BI;Duda, JE;Lee, VMY
通讯作者：
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影响因子：
6
作者：
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DOI：
10.1073/pnas.0404650101
发表时间：
2004-08-17
影响因子：
11.1
作者：
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通讯作者：
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作者：
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影响因子：
16.6
作者：
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