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Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue

Author

Listed:
  • Dhruva D. Dhavale

    (Washington University School of Medicine)

  • Alexander M. Barclay

    (University of Illinois at Urbana-Champaign)

  • Collin G. Borcik

    (University of Wisconsin-Madison)

  • Katherine Basore

    (Washington University School of Medicine)

  • Deborah A. Berthold

    (University of Illinois at Urbana-Champaign)

  • Isabelle R. Gordon

    (Washington University School of Medicine)

  • Jialu Liu

    (Washington University School of Medicine)

  • Moses H. Milchberg

    (University of Wisconsin-Madison)

  • Jennifer Y. O’Shea

    (Washington University School of Medicine)

  • Michael J. Rau

    (Washington University School of Medicine)

  • Zachary Smith

    (Washington University School of Medicine)

  • Soumyo Sen

    (University of Illinois at Urbana-Champaign)

  • Brock Summers

    (Washington University School of Medicine)

  • John Smith

    (University of Illinois at Urbana-Champaign)

  • Owen A. Warmuth

    (University of Wisconsin-Madison)

  • Richard J. Perrin

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Joel S. Perlmutter

    (Washington University School of Medicine
    Washington University School of Medicine)

  • Qian Chen

    (University of Illinois at Urbana-Champaign)

  • James A. J. Fitzpatrick

    (Washington University School of Medicine)

  • Charles D. Schwieters

    (National Institutes of Health)

  • Emad Tajkhorshid

    (University of Illinois at Urbana-Champaign)

  • Chad M. Rienstra

    (University of Illinois at Urbana-Champaign
    University of Wisconsin-Madison
    University of Wisconsin-Madison
    University of Wisconsin-Madison)

  • Paul T. Kotzbauer

    (Washington University School of Medicine)

Abstract

The defining feature of Parkinson disease (PD) and Lewy body dementia (LBD) is the accumulation of alpha-synuclein (Asyn) fibrils in Lewy bodies and Lewy neurites. Here we develop and validate a method to amplify Asyn fibrils extracted from LBD postmortem tissue samples and use solid state nuclear magnetic resonance (SSNMR) studies to determine atomic resolution structure. Amplified LBD Asyn fibrils comprise a mixture of single protofilament and two protofilament fibrils with very low twist. The protofilament fold is highly similar to the fold determined by a recent cryo-electron microscopy study for a minority population of twisted single protofilament fibrils extracted from LBD tissue. These results expand the structural characterization of LBD Asyn fibrils and approaches for studying disease mechanisms, imaging agents and therapeutics targeting Asyn.

Suggested Citation

  • Dhruva D. Dhavale & Alexander M. Barclay & Collin G. Borcik & Katherine Basore & Deborah A. Berthold & Isabelle R. Gordon & Jialu Liu & Moses H. Milchberg & Jennifer Y. O’Shea & Michael J. Rau & Zacha, 2024. "Structure of alpha-synuclein fibrils derived from human Lewy body dementia tissue," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46832-5
    DOI: 10.1038/s41467-024-46832-5
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    References listed on IDEAS

    as
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