Home > Publications Database > Acetylation discriminates disease-specific tau deposition. > print

001     264175
005     20240112171321.0
024 7 _ |a 10.1038/s41467-023-41672-1
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037 _ _ |a DZNE-2023-00955
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100 1 _ |a Chakraborty, Pijush
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245 _ _ |a Acetylation discriminates disease-specific tau deposition.
260 _ _ |a [London]
|c 2023
|b Nature Publishing Group UK
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520 _ _ |a 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.
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650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a 14-3-3 Proteins
|2 MeSH
650 _ 2 |a Acetylation
|2 MeSH
650 _ 2 |a Alzheimer Disease
|2 MeSH
650 _ 2 |a tau Proteins
|2 MeSH
650 _ 2 |a Tauopathies
|2 MeSH
650 _ 7 |a 14-3-3 Proteins
|2 NLM Chemicals
650 _ 7 |a tau Proteins
|2 NLM Chemicals
650 _ 7 |a MAPT protein, human
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700 1 _ |a Rivière, Gwladys
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700 1 _ |a Hebestreit, Alina
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700 1 _ |a de Opakua, Alain Ibáñez
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700 1 _ |a Vorberg, Ina M
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700 1 _ |a Andreas, Loren B
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700 1 _ |a Zweckstetter, Markus
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773 _ _ |a 10.1038/s41467-023-41672-1
|g Vol. 14, no. 1, p. 5919
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|t Nature Communications
|v 14
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856 4 _ |y OpenAccess
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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