Journal article

Small Heat-shock Proteins Prevent -Synuclein Aggregation via Transient Interactions and Their Efficacy Is Affected by the Rate of Aggregation

Dezerae Cox, Emily Selig, Michael DW Griffin, John A Carver, Heath Ecroyd

JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2016

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 s..

View full abstract

Grants

Awarded by Australian Research Council


Awarded by Australian National Health and Medical Research Council


Funding Acknowledgements

This work was supported in part by grants from the Australian Department of Health and Aging and the University of Wollongong. The authors declare that they have no conflicts of interest with the contents of this article.r Supported by an Australian Postgraduate Award.r Supported by Australian Research Council Future Fellowships FT110100586 and FT140100544.r Supported by an Australian National Health and Medical Research Council project Grant 1068087.