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    Hsp70 alters tau function and aggregation in an isoform specific manner

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    Voss_ACS_2012.pdf (906.9Kb)
    Issue Date
    2012-01-31
    Author
    Voss, Kellen R.
    Combs, Benjamin
    Patterson, Kristina
    Binder, Lester I.
    Gamblin, Truman Chris
    Publisher
    ACS
    Type
    Article
    Article Version
    Scholarly/refereed, author accepted manuscript
    Rights
    Copyright © 2012 American Chemical Society
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    Abstract
    Tauopathies are characterized by abnormal aggregation of the microtubule associated protein tau. This aggregation is thought to occur when tau undergoes shifts from its native conformation to one that exposes hydrophobic areas on separate monomers, allowing contact and subsequent association into oligomers and filaments. Molecular chaperones normally function by binding to exposed hydrophobic stretches on proteins and assisting in their refolding. Chaperones of the heat shock protein 70 (Hsp70) family have been implicated in the prevention of abnormal tau aggregation in adult neurons. Tau exists as six alternatively spliced isoforms, and all six isoforms appear capable of forming the pathological aggregates seen in Alzheimer's disease. Because tau isoforms differ in primary sequence, we sought to determine whether Hsp70 would differentially affect the aggregation and microtubule assembly characteristics of the various tau isoforms. We found that Hsp70 inhibits tau aggregation directly, and not through inducer mediated effects. We also determined that Hsp70 inhibits the aggregation of each individual tau isoform and was more effective at inhibiting the three repeat isoforms. . Finally, all tau isoforms robustly induced microtubule formation while in the presence of Hsp70. The results presented herein indicate that Hsp70 affects tau isoform dysfunction while having very little impact on the normal function of tau to mediate microtubule assembly. This indicates that targeting Hsp70 to tau may provide a therapeutic approach for the treatment of tauopathies that avoids disruption of normal tau function.
    URI
    http://hdl.handle.net/1808/23689
    DOI
    https://doi.org/10.1021/bi2018078
    Collections
    • Molecular Biosciences Scholarly Works [572]
    Citation
    Voss, K., Combs, B., Patterson, K., Binder, L. I., & Gamblin, T. C. (2012). Hsp70 alters tau function and aggregation in an isoform specific manner. Biochemistry, 51(4), 888–898. http://doi.org/10.1021/bi2018078

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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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