The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system

Itika Saha; Patricia Yuste-Checa; Miguel Da Silva Padilha; Qiang Guo; Roman Körner; Hauke Holthusen; Victoria A. Trinkaus; Irina Dudanova; Rubén Fernández-Busnadiego; Wolfgang Baumeister; David W. Sanders; Saurabh Gautam; Marc I. Diamond; F. Ulrich Hartl; Mark S. Hipp

doi:10.1038/s41467-023-36058-2

Nature Communications (Feb 2023)

The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system

Itika Saha,
Patricia Yuste-Checa,
Miguel Da Silva Padilha,
Qiang Guo,
Roman Körner,
Hauke Holthusen,
Victoria A. Trinkaus,
Irina Dudanova,
Rubén Fernández-Busnadiego,
Wolfgang Baumeister,
David W. Sanders,
Saurabh Gautam,
Marc I. Diamond,
F. Ulrich Hartl,
Mark S. Hipp

Affiliations

Itika Saha: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry
Patricia Yuste-Checa: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry
Miguel Da Silva Padilha: Molecular Neurodegeneration Group, Max Planck Institute for Biological Intelligence
Qiang Guo: Department of Structural Molecular Biology, Max Planck Institute of Biochemistry
Roman Körner: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry
Hauke Holthusen: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry
Victoria A. Trinkaus: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry
Irina Dudanova: Molecular Neurodegeneration Group, Max Planck Institute for Biological Intelligence
Rubén Fernández-Busnadiego: Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network
Wolfgang Baumeister: Department of Structural Molecular Biology, Max Planck Institute of Biochemistry
David W. Sanders: Center for Alzheimer’s and Neurodegenerative Diseases, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center
Saurabh Gautam: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry
Marc I. Diamond: Center for Alzheimer’s and Neurodegenerative Diseases, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center
F. Ulrich Hartl: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry
Mark S. Hipp: Department of Cellular Biochemistry, Max Planck Institute of Biochemistry

DOI: https://doi.org/10.1038/s41467-023-36058-2
Journal volume & issue: Vol. 14, no. 1
pp. 1 – 17

Abstract

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Tau aggregates are associated with several neurodegenerative disorders. In this work, I. Saha and colleagues show that valosin-containing protein (VCP) recruited to Tau fibrils disaggregates them. However, this process comes at a cost: it generates seeding-active Tau species as byproduct.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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