期刊
JOURNAL OF NEUROCHEMISTRY
卷 89, 期 2, 页码 454-463出版社
BLACKWELL PUBLISHING LTD
DOI: 10.1111/j.1471-4159.2004.02356.x
关键词
antibodies mechanism and therapeutic; anti-prion agent; prion disease
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 PrPSc 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 PrPSc formation in prion-infected neuroblastoma cells but also decreased the PrPC levels in non-infected N2a cells. In addition, treatment with both SAF34 and SAF61 antibodies decreased PrPC and PrPSc 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 PrPSc in cells is directly coupled to PrPC degradation by reducing the half-life of the PrPC protein.
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