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Inhibition of α-synuclein aggregation by small heat shock proteins.
- Source :
- Proteins; Oct2011, Vol. 79 Issue 10, p2956-2967, 12p
- Publication Year :
- 2011
-
Abstract
- 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. Proteins 2011; © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08873585
- Volume :
- 79
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Proteins
- Publication Type :
- Academic Journal
- Accession number :
- 65278826
- Full Text :
- https://doi.org/10.1002/prot.23152