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Acetylation discriminates disease-specific tau deposition

Author

Listed:
  • Pijush Chakraborty

    (German Center for Neurodegenerative Diseases (DZNE))

  • Gwladys Rivière

    (German Center for Neurodegenerative Diseases (DZNE))

  • Alina Hebestreit

    (German Center for Neurodegenerative Diseases (DZNE))

  • Alain Ibáñez Opakua

    (German Center for Neurodegenerative Diseases (DZNE))

  • Ina M. Vorberg

    (German Center for Neurodegenerative Diseases (DZNE)
    Rheinische Friedrich-Wilhelms-Universität)

  • Loren B. Andreas

    (Max Planck Institute for Multidisciplinary Sciences)

  • Markus Zweckstetter

    (German Center for Neurodegenerative Diseases (DZNE)
    Max Planck Institute for Multidisciplinary Sciences)

Abstract

Pathogenic aggregation of the protein tau is a hallmark of Alzheimer’s disease and several other tauopathies. Tauopathies are characterized by the deposition of specific tau isoforms as disease-related tau filament structures. The molecular processes that determine isoform-specific deposition of tau are however enigmatic. Here we show that acetylation of tau discriminates its isoform-specific aggregation. We reveal that acetylation strongly attenuates aggregation of four-repeat tau protein, but promotes amyloid formation of three-repeat tau. We further identify acetylation of lysine 298 as a hot spot for isoform-specific tau aggregation. Solid-state NMR spectroscopy demonstrates that amyloid fibrils formed by unmodified and acetylated three-repeat tau differ in structure indicating that site-specific acetylation modulates tau structure. The results implicate acetylation as a critical regulator that guides the selective aggregation of three-repeat tau and the development of tau isoform-specific neurodegenerative diseases.

Suggested Citation

  • Pijush Chakraborty & Gwladys Rivière & Alina Hebestreit & Alain Ibáñez Opakua & Ina M. Vorberg & Loren B. Andreas & Markus Zweckstetter, 2023. "Acetylation discriminates disease-specific tau deposition," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41672-1
    DOI: 10.1038/s41467-023-41672-1
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