抗朊蛋白抗体通过加速朊蛋白C的降解来阻断朊病毒感染细胞培养物中的朊病毒蛋白Sc复制。
Anti-PrP antibodies block PrPSc replication in prion-infected cell cultures by accelerating PrPC degradation.
作者信息
Perrier Véronique, Solassol Jérôme, Crozet Carole, Frobert Yveline, Mourton-Gilles Chantal, Grassi Jacques, Lehmann Sylvain
机构信息
Institut de Génétique Humaine, Montpellier, France.
出版信息
J Neurochem. 2004 Apr;89(2):454-63. doi: 10.1111/j.1471-4159.2004.02356.x.
Abstract
The use of anti-PrP antibodies represents one of the most promising strategies for the treatment of prion diseases. In the present study, we screened various anti-PrP antibodies with the aim of identifying those that would block PrP(Sc) replication in prion-infected cell culture. Two antibodies, SAF34 recognizing the flexible octarepeats region on HuPrP protein, and SAF61 directed against PrP amino acid residues (144-152), not only inhibited PrP(Sc) formation in prion-infected neuroblastoma cells but also decreased the PrP(C) levels in non-infected N2a cells. In addition, treatment with both SAF34 and SAF61 antibodies decreased PrP(C) and PrP(Sc) levels in the cells synergistically. In the presence of both antibodies, our results showed that the mode of action which leads to the disappearance of PrP(Sc) in cells is directly coupled to PrP(C) degradation by reducing the half-life of the PrP(C) protein.
摘要
使用抗PrP抗体是治疗朊病毒疾病最有前景的策略之一。在本研究中，我们筛选了多种抗PrP抗体，目的是鉴定出那些能在朊病毒感染的细胞培养物中阻断PrP(Sc)复制的抗体。两种抗体，识别HuPrP蛋白上柔性八肽重复区域的SAF34和针对PrP氨基酸残基（144 - 152）的SAF61，不仅抑制了朊病毒感染的神经母细胞瘤细胞中PrP(Sc)的形成，还降低了未感染的N2a细胞中的PrP(C)水平。此外，用SAF34和SAF61抗体处理可协同降低细胞中的PrP(C)和PrP(Sc)水平。在两种抗体都存在的情况下，我们的结果表明，导致细胞中PrP(Sc)消失的作用模式与通过缩短PrP(C)蛋白半衰期直接导致PrP(C)降解有关。
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