Academic Journal
Molecular Plasticity Regulates Oligomerization and Cytotoxicity of the Multipeptide-length Amyloid-beta Peptide Pool
| العنوان: | Molecular Plasticity Regulates Oligomerization and Cytotoxicity of the Multipeptide-length Amyloid-beta Peptide Pool |
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| المؤلفون: | Vandersteen, A., Masman, M.F., De Baets, G., Jonckheere, W., van der Werf, K., Marrink, S.J., Rozenski, J., Benilova, I., De Strooper, B., Subramaniam, V., Schymkowitz, J., Rousseau, F., Broersen, K. |
| المصدر: | Journal of Biological Chemistry, 287, 44, pp. 36732-43 ; http://www.ncbi.nlm.nih.gov/pubmed/22992745 |
| سنة النشر: | 2012 |
| المجموعة: | Radboud University: DSpace |
| مصطلحات موضوعية: | NCMLS 2: Immune Regulation |
| الوصف: | Contains fulltext : 108708.pdf (Publisher’s version ) (Open Access) ; Current therapeutic approaches under development for Alzheimer disease, including gamma-secretase modulating therapy, aim at increasing the production of Abeta(1-38) and Abeta(1-40) at the cost of longer Abeta peptides. Here, we consider the aggregation of Abeta(1-38) and Abeta(1-43) in addition to Abeta(1-40) and Abeta(1-42), in particular their behavior in mixtures representing the complex in vivo Abeta pool. We demonstrate that Abeta(1-38) and Abeta(1-43) aggregate similar to Abeta(1-40) and Abeta(1-42), respectively, but display a variation in the kinetics of assembly and toxicity due to differences in short timescale conformational plasticity. In biologically relevant mixtures of Abeta, Abeta(1-38) and Abeta(1-43) significantly affect the behaviors of Abeta(1-40) and Abeta(1-42). The short timescale conformational flexibility of Abeta(1-38) is suggested to be responsible for enhancing toxicity of Abeta(1-40) while exerting a cyto-protective effect on Abeta(1-42). Our results indicate that the complex in vivo Abeta peptide array and variations thereof is critical in Alzheimer disease, which can influence the selection of current and new therapeutic strategies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| Relation: | https://repository.ubn.ru.nl//bitstream/handle/2066/108708/108708.pdf; http://hdl.handle.net/2066/108708 |
| DOI: | 10.1074/jbc.M112.394635 |
| الاتاحة: | http://hdl.handle.net/2066/108708 https://repository.ubn.ru.nl//bitstream/handle/2066/108708/108708.pdf https://doi.org/10.1074/jbc.M112.394635 |
| رقم الانضمام: | edsbas.E077C734 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1074/jbc.M112.394635 |
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