التفاصيل البيبلوغرافية
| العنوان: |
Inhibition of α-synuclein aggregation by small heat shock proteins |
| المؤلفون: |
Bruinsma, Ilona B., Bruggink, Kim A., Kinast, Karsten, Versleijen, Alexandra A.M., Segers-Nolten, Ine M.J., Subramaniam, Vinod, Kuiperij, H. Bea, Boelens, Wilbert, Waal, Robert M.W. de, Verbeek, Marcel M. |
| بيانات النشر: |
Liss |
| سنة النشر: |
2011 |
| المجموعة: |
University of Twente Publications |
| الوصف: |
The fibrillization of α-synuclein (α-syn) is a key event in the pathogenesis of α-synucleinopathies. Mutant α-syn (A53T, A30P, or E46K), each linked to familial Parkinson's disease, has altered aggregation properties, fibril morphologies, and fibrillization kinetics. Besides α-syn, Lewy bodies also contain several associated proteins including small heat shock proteins (sHsps). Since α-syn accumulates intracellularly, molecular chaperones like sHsps may regulate α-syn folding and aggregation. Therefore, we investigated if the sHsps αB-crystallin, Hsp27, Hsp20, HspB8, and HspB2B3 bind to α-syn and affect α-syn aggregation. We demonstrate that all sHsps bind to the various α-syns, although the binding kinetics suggests a weak and transient interaction only. Despite this transient interaction, the various sHsps inhibited mature α-syn fibril formation as shown by a Thioflavin T assay and atomic force microscopy. Interestingly, HspB8 was the most potent sHsp in inhibiting mature fibril formation of both wild-type and mutant α-syn. In conclusion, sHsps may regulate α-syn aggregation and, therefore, optimization of the interaction between sHsps and α-syn may be an interesting target for therapeutic intervention in the pathogenesis of α-synucleinopathies |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
http://doc.utwente.nl/96431/1/Bruinsma%20%282011%29%20Proteins-Struct-Funct-Bioinform%2079_2956-2967.pdfTest; http://purl.utwente.nl/publications/96431Test |
| الإتاحة: |
http://purl.utwente.nl/publications/96431Test |
| رقم الانضمام: |
edsbas.BA5A2B84 |
| قاعدة البيانات: |
BASE |
