Enrichment of prion protein in exosomes derived from ovine cerebral spinal fluid

Enrichment of prion protein in exosomes derived from ovine cerebral spinal fluid
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DOI:
10.1016/j.vetimm.2008.04.002
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发表时间:
2008-08-15
影响因子:
1.8
通讯作者:
Hill, Andrew F.
Hill, Andrew F.
中科院分区:
农林科学3区
文献类型:
--
作者:
Vella, Laura J.;Greenwood, Deanne L. V.;Hill, Andrew F.

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朊病毒疾病是影响人类和包括羊和牛在内的多种动物物种的传染性神经退行性疾病。传播媒介,朊病毒,是宿主编码的细胞朊病毒蛋白(PrPC)的异常折叠形式(PrPSc)。朊病毒蛋白在这些疾病易感物种体液中的分布对人类健康和朊病毒病的医源性传播具有重要意义。除了已确认为朊病毒感染来源的血液外,目前尚不清楚其他哪些体液具有重大传播风险。在目前的研究中,我们检测了两种羊的伪传入液,淋巴液和脑脊液(CSF),以检测外泌体的存在和正常细胞形式的朊病毒蛋白(PrPC)的同时富集。在这里,我们证明了从绵羊分离的伪传入淋巴和脑脊液中存在外泌体。在脑脊液衍生的外泌体中,我们能够在未分离的脑脊液上发现PrPC的富集。这一实验方法表明,脑脊液衍生的外泌体可以作为一种检测异常形式的朊病毒蛋白的新手段,并提供这些囊泡与朊病毒疾病发病机制之间的体内联系。(C) 2008年Elsevier B.V.出版
Prion diseases are transmissible neurodegenerative disorders affecting humans and a wide variety of animal species including sheep and cattle. The transmissible agent, the prion, is an abnormally folded form (PrPSc) of the host encoded cellular prion protein (PrPC). Distribution of the prion protein in the fluids of species Susceptible to these diseases is of importance to human health and the iatrogenic spread of prion disease. Aside from blood which is confirmed to be a source of prion infectivity, it is Currently unclear which other body fluids harbor a significant transmission risk. In the Current study we examined two ovine fluids pseudo-afferent, lymph and cerebral spinal fluid (CSF), for the presence of exosomes and concurrent enrichment of the normal, cellular form of the prion protein (PrPC). Here we demonstrate the existence of exosomes in both pseudo-afferent lymph and CSF isolated from sheep. In the CSF derived exosomes we were able to show an enrichment of PrPC over Unfractionated CSF This experimental approach suggests that CSF derived exosomes could be Used as a novel means of detecting abnormal forms of the prion protein and provide an in vivo link between these vesicles and prion disease pathogenesis. (C) 2008 Published by Elsevier B.V.