Heat Shock Protein 70 Prevents both Tau Aggregation and the Inhibitory Effects of Preexisting Tau Aggregates on Fast Axonal Transport

View/ Open
Issue Date
2011-11-29Author
Patterson, Kristina
Ward, Sarah M.
Combs, Benjamin
Voss, Kellen R.
Kanaan, Nicholas M.
Morfini, Gerardo
Brady, Scott T.
Gamblin, Truman Chris
Binder, Lester I.
Publisher
ACS
Type
Article
Article Version
Scholarly/refereed, author accepted manuscript
Rights
Copyright © 2011 American Chemical Society
Metadata
Show full item recordAbstract
Aggregation and accumulation of the microtubule-associated protein tau are associated with
cognitive decline and neuronal degeneration in Alzheimer's disease and other tauopathies. Thus,
preventing the transition of tau from a soluble state to insoluble aggregates and/or reversing the
toxicity of existing aggregates would represent a reasonable therapeutic strategy for treating these
neurodegenerative diseases. Here we demonstrate that molecular chaperones of the heat shock
protein 70 (Hsp70) family are potent inhibitors of tau aggregation in vitro, preventing the
formation of both mature fibrils and oligomeric intermediates. Remarkably, addition of Hsp70 to a
mixture of oligomeric and fibrillar tau aggregates prevents the toxic effect of these tau species on
fast axonal transport, a critical process for neuronal function. When incubated with preformed tau
aggregates, Hsp70 preferentially associated with oligomeric over fibrillar tau, suggesting that
prefibrillar oligomeric tau aggregates play a prominent role in tau toxicity. Taken together, our
data provide a novel molecular basis for the protective effect of Hsp70 in tauopathies.
Collections
Citation
Patterson, K. R., Ward, S. M., Combs, B., Voss, K., Kanaan, N. M., Morfini, G., … Binder, L. I. (2011). Heat Shock Protein 70 Prevents both Tau Aggregation and the Inhibitory Effects of Preexisting Tau Aggregates on Fast Axonal Transport. Biochemistry, 50(47), 10300–10310. http://doi.org/10.1021/bi2009147
Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.