1. Small Heat-shock Proteins Prevent α-Synuclein Aggregation via Transient Interactions and Their Efficacy Is Affected by the Rate of Aggregation.
- Author
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Cox, Dezerae, Selig, Emily, Griffin, Michael D. W., Carver, John A., and Ecroyd, Heath
- Subjects
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HSP70 heat-shock proteins , *NEURODEGENERATION , *MOLECULAR chaperones , *CELL analysis , *CRYSTAL structure , *DIAGNOSIS - Abstract
The aggregation of α-synuclein (α-syn) into amyloid fibrils is associated with neurodegenerative diseases, collectively referred to as the α-synucleinopathies. In vivo, molecular chaperones, such as the small heat-shock proteins (sHsps), normally act to prevent protein aggregation; however, it remains to be determined how aggregation-prone α-syn evades sHsp chaperone action leading to its disease-associated deposition. This work examines the molecular mechanism by which two canonical sHsps,αB-crystallin (αB-c) and Hsp27, interact with aggregation-prone α-syn to prevent its aggregation in vitro. Both sHsps are very effective inhibitors of α-syn aggregation, but no stable complex between the sHsps andα-syn was detected, indicating that the sHsps inhibit α-syn aggregation via transient interactions. Moreover, the ability of these sHsps to prevent α-syn aggregation was dependent on the kinetics of aggregation; the faster the rate of aggregation (shorter the lag phase), the less effective the sHsps were at inhibiting fibril formation of α-syn. Thus, these findings indicate that the rate at whichα-syn aggregates in cells may be a significant factor in how it evades sHsp chaperone action in the α-synucleinopathies. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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