Academic Journal
Human Anti-prion Antibodies Block Prion Peptide Fibril Formation and Neurotoxicity
| العنوان: | Human Anti-prion Antibodies Block Prion Peptide Fibril Formation and Neurotoxicity |
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| المؤلفون: | Wei, Xing, Roettger, Yvonne, Tan, Bailin, He, Yongzheng, Dodel, Richard, Hampel, Harald, Wei, Gang, Haney, Jillian, Gu, Huiying, Johnstone, Brian H., Liu, Junyi, Farlow, Martin R., Du, Yansheng |
| المساهمون: | Du, YS (reprint author), Indiana Univ, Dept Neurol, Sch Med, 975 W Walnut St,IB 457, Indianapolis, IN 46202 USA., Indiana Univ Sch Med, Dept Neurol, Indianapolis, IN 46202 USA., Univ Marburg, Dept Neurol, D-35039 Marburg, Germany., Goethe Univ Frankfurt, Dept Psychiat, D-60528 Frankfurt, Germany., Peking Univ, Sch Pharmaceut Sci, Beijing 100083, Peoples R China., Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA., Indiana Univ, Dept Neurol, Sch Med, 975 W Walnut St,IB 457, Indianapolis, IN 46202 USA. |
| المصدر: | SCI ; EI |
| بيانات النشر: | journal of biological chemistry |
| سنة النشر: | 2012 |
| المجموعة: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| مصطلحات موضوعية: | STRAUSSLER-SCHEINKER-DISEASE, CEREBELLAR GRANULE NEURONS, AMYLOID-BETA-PEPTIDE, PROTEIN-FRAGMENT, ALZHEIMERS-DISEASE, INTRAVENOUS IMMUNOGLOBULINS, MONOCLONAL-ANTIBODIES, CYSTEINE PROTEASE, CELLS, PRP |
| الوصف: | 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. ; Biochemistry & Molecular Biology ; SCI(E) ; EI ; 9 ; ARTICLE ; 16 ; 12858-12866 ; 287 |
| نوع الوثيقة: | journal/newspaper |
| اللغة: | English |
| تدمد: | 0021-9258 |
| Relation: | JOURNAL OF BIOLOGICAL CHEMISTRY.2012,287,(16),12858-12866.; 888707; http://hdl.handle.net/20.500.11897/393843; WOS:000302903700025 |
| DOI: | 10.1074/jbc.M111.255836 |
| الاتاحة: | https://hdl.handle.net/20.500.11897/393843 https://doi.org/10.1074/jbc.M111.255836 |
| رقم الانضمام: | edsbas.1DA778CA |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 00219258 |
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| DOI: | 10.1074/jbc.M111.255836 |