Academic Journal
Nanobodies raised against monomeric alpha-synuclein inhibit fibril formation and destabilize toxic oligomeric species
| العنوان: | Nanobodies raised against monomeric alpha-synuclein inhibit fibril formation and destabilize toxic oligomeric species |
|---|---|
| المؤلفون: | Iljina, M, Hong, L, Horrocks, MH, Ludtmann, MH, Choi, ML, Hughes, CD, Ruggeri, FS, Guilliams, T, Buell, AK, Lee, J-E, Gandhi, S, Lee, SF, Bryant, CE, Vendruscolo, M, Knowles, TPJ, Dobson, CM, De Genst, E, Klenerman, D |
| المصدر: | BMC Biology , 15 , Article 57. (2017) |
| بيانات النشر: | BIOMED CENTRAL LTD |
| سنة النشر: | 2017 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Biology, Life Sciences & Biomedicine - Other Topics, Protein aggregation, Amyloid toxicity, Neurodegeneration, Aggregation inhibitors, Antibody, Single-molecule fluorescence, SPORADIC PARKINSONS-DISEASE, MULTIPLE SYSTEM ATROPHY, ANTIBODY FRAGMENTS, LEWY BODIES, AGGREGATION, PATHOLOGY, BRAIN, IMMUNOREACTIVITY |
| الوصف: | BACKGROUND: The aggregation of the protein ɑ-synuclein (ɑS) underlies a range of increasingly common neurodegenerative disorders including Parkinson’s disease. One widely explored therapeutic strategy for these conditions is the use of antibodies to target aggregated ɑS, although a detailed molecular-level mechanism of the action of such species remains elusive. Here, we characterize ɑS aggregation in vitro in the presence of two ɑS-specific single-domain antibodies (nanobodies), NbSyn2 and NbSyn87, which bind to the highly accessible C-terminal region of ɑS. RESULTS: We show that both nanobodies inhibit the formation of ɑS fibrils. Furthermore, using single-molecule fluorescence techniques, we demonstrate that nanobody binding promotes a rapid conformational conversion from more stable oligomers to less stable oligomers of ɑS, leading to a dramatic reduction in oligomer-induced cellular toxicity. CONCLUSIONS: The results indicate a novel mechanism by which diseases associated with protein aggregation can be inhibited, and suggest that NbSyn2 and NbSyn87 could have significant therapeutic potential. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| Relation: | https://discovery.ucl.ac.uk/id/eprint/1565307/1/s12915-017-0390-6.pdf; https://discovery.ucl.ac.uk/id/eprint/1565307/ |
| الاتاحة: | https://discovery.ucl.ac.uk/id/eprint/1565307/1/s12915-017-0390-6.pdf https://discovery.ucl.ac.uk/id/eprint/1565307/ |
| Rights: | open |
| رقم الانضمام: | edsbas.78556AB5 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |