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The prion protein in neuroimmune crosstalk.
Neurochemistry international ( IF 4.4 ) Pub Date : 2018-11-15 , DOI: 10.1016/j.neuint.2018.11.010
Øyvind Salvesen 1 , Jörg Tatzelt 2 , Michael A Tranulis 3
Affiliation  

The cellular prion protein (PrPC) is a medium-sized glycoprotein, attached to the cell surface by a glycosylphosphatidylinositol anchor. PrPC is encoded by a single-copy gene, PRNP, which is abundantly expressed in the central nervous system and at lower levels in non-neuronal cells, including those of the immune system. Evidence from experimental knockout of PRNP in rodents, goats, and cattle and the occurrence of a nonsense mutation in goat that prevents synthesis of PrPC, have shown that the molecule is non-essential for life. Indeed, no easily recognizable phenotypes are associate with a lack of PrPC, except the potentially advantageous trait that animals without PrPC cannot develop prion disease. This is because, in prion diseases, PrPC converts to a pathogenic "scrapie" conformer, PrPSc, which aggregates and eventually induces neurodegeneration. In addition, endogenous neuronal PrPC serves as a toxic receptor to mediate prion-induced neurotoxicity. Thus, PrPC is an interesting target for treatment of prion diseases. Although loss of PrPC has no discernable effect, alteration of its normal physiological function can have very harmful consequences. It is therefore important to understand cellular processes involving PrPC, and research of this topic has advanced considerably in the past decade. Here, we summarize data that indicate the role of PrPC in modulating immune signaling, with emphasis on neuroimmune crosstalk both under basal conditions and during inflammatory stress.

中文翻译:

neuro病毒蛋白在神经免疫串扰中。

细胞病毒蛋白(PrPC)是中等大小的糖蛋白,通过糖基磷脂酰肌醇锚定物附着在细胞表面。PrPC由单拷贝基因PRNP编码,该基因在中枢神经系统中大量表达,在非神经元细胞(包括免疫系统细胞)中较低水平表达。从啮齿动物,山羊和牛的PRNP实验性敲除的证据以及山羊中无意义的突变的发生阻止了PrPC的合成,这些证据表明该分子对于生命不是必需的。的确,除了缺乏PrPC的动物无法发展病毒疾病的潜在优势特征外,没有任何易于识别的表型与PrPC的缺乏有关。这是因为在病毒疾病中,PrPC会转化为致病性的“ sc痒”构象体PrPSc,聚集并最终导致神经退行性变。此外,内源性神经元PrPC充当介导病毒诱导的神经毒性的毒性受体。因此,PrPC是治疗病毒疾病的有趣目标。尽管PrPC的丧失没有明显的作用,但是其正常生理功能的改变可能会带来非常有害的后果。因此,重要的是要了解涉及PrPC的细胞过程,并且在过去十年中,对该主题的研究已取得了很大进展。在这里,我们总结了表明PrPC在调节免疫信号中的作用的数据,重点是在基础条件下和炎性应激期间的神经免疫串扰。PrPC是治疗of病毒疾病的有趣目标。尽管PrPC的丧失没有明显的作用,但是其正常生理功能的改变可能会带来非常有害的后果。因此,重要的是要了解涉及PrPC的细胞过程,并且在过去十年中,对该主题的研究已取得了很大进展。在这里,我们总结了表明PrPC在调节免疫信号中的作用的数据,重点是在基础条件下和炎性应激期间的神经免疫串扰。PrPC是治疗of病毒疾病的有趣目标。尽管PrPC的丧失没有明显的作用,但是其正常生理功能的改变可能会带来非常有害的后果。因此,重要的是要了解涉及PrPC的细胞过程,并且在过去十年中,对该主题的研究已取得了很大进展。在这里,我们总结了表明PrPC在调节免疫信号中的作用的数据,重点是在基础条件下和炎性应激期间的神经免疫串扰。
更新日期:2018-11-15
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