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学科主题: 药学
题名:
Human Anti-prion Antibodies Block Prion Peptide Fibril Formation and Neurotoxicity
作者: Wei, Xing1; Roettger, Yvonne2; Tan, Bailin1; He, Yongzheng1; Dodel, Richard2; Hampel, Harald3; Wei, Gang1; Haney, Jillian1; Gu, Huiying1; Johnstone, Brian H.5; Liu, Junyi4; Farlow, Martin R.1; Du, Yansheng1
刊名: JOURNAL OF BIOLOGICAL CHEMISTRY
发表日期: 2012-04-13
DOI: 10.1074/jbc.M111.255836
卷: 287, 期:16, 页:12858-12866
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: STRAUSSLER-SCHEINKER-DISEASE ; CEREBELLAR GRANULE NEURONS ; AMYLOID-BETA-PEPTIDE ; PROTEIN-FRAGMENT ; ALZHEIMERS-DISEASE ; INTRAVENOUS IMMUNOGLOBULINS ; MONOCLONAL-ANTIBODIES ; CYSTEINE PROTEASE ; CELLS ; PRP
英文摘要:

Prion diseases are a group of rare, fatal neurodegenerative disorders associated with a conformational transformation of the cellular prion protein (PrPC) into a self-replicating and proteinase K-resistant conformer, termed scrapie PrP (PrPSc). Aggregates of PrPSc deposited around neurons lead to neuropathological alterations. Currently, there is no effective treatment for these fatal illnesses; thus, the development of an effective therapy is a priority. PrP peptide-based ELISA assay methods were developed for detection and immunoaffinity chromatography capture was developed for purification of naturally occurring PrP peptide autoantibodies present in human CSF, individual donor serum, and commercial preparations of pooled intravenous immunoglobulin (IVIg). The ratio of anti-PrP autoantibodies (PrP-AA) to total IgG was similar to 1:1200. The binding epitope of purified PrP-AA was mapped to an N-terminal region comprising the PrP amino acid sequence KTNMK. Purified PrP-AA potently blocked fibril formation by a toxic 21-amino acid fragment of the PrP peptide containing the amino acid alanine to valine substitution corresponding to position 117 of the full-length peptide (A117V). Furthermore, PrP-AA attenuated the neurotoxicity of PrP(A117V) and wildtype peptides in rat cerebellar granule neuron (CGN) cultures. In contrast, IgG preparations depleted of PrP-AA had little effect on PrP fibril formation or PrP neurotoxicity. The specificity of PrP-AA was demonstrated by immunoprecipitating PrP protein in brain tissues of transgenic mice expressing the human PrP(A117V) epitope and Sc237 hamster. Based on these intriguing findings, it is suggested that human PrP-AA may be useful for interfering with the pathogenic effects of pathogenic prion proteins and, thereby has the potential to be an effective means for preventing or attenuating human prion disease progression.

语种: 英语
WOS记录号: WOS:000302903700025
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51123
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Univ Marburg, Dept Neurol, D-35039 Marburg, Germany
2.Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA
3.Goethe Univ Frankfurt, Dept Psychiat, D-60528 Frankfurt, Germany
4.Peking Univ, Sch Pharmaceut Sci, Beijing 100083, Peoples R China
5.Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA

Recommended Citation:
Wei, Xing,Roettger, Yvonne,Tan, Bailin,et al. Human Anti-prion Antibodies Block Prion Peptide Fibril Formation and Neurotoxicity[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2012,287(16):12858-12866.
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