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

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    Patterson_ACS_2011.pdf (1.826Mb)
    Issue Date
    2011-11-29
    Author
    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
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    Abstract
    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.
    URI
    http://hdl.handle.net/1808/23688
    DOI
    https://doi.org/10.1021/bi2009147
    Collections
    • Molecular Biosciences Scholarly Works [582]
    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

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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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