| |  Online-Ressource |
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| Verfasst von: | Nachman, Eliana [VerfasserIn]  |
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| | Wentink, Anne [VerfasserIn] |
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| | Madiona, Karine [VerfasserIn] |
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| | Bousset, Luc [VerfasserIn] |
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| | Katsinelos, Taxiarchis [VerfasserIn] |
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| | Allinson, Kieren [VerfasserIn] |
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| | Kampinga, Harm [VerfasserIn] |
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| | McEwan, William A. [VerfasserIn] |
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| | Jahn, Thomas R. [VerfasserIn] |
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| | Melki, Ronald [VerfasserIn] |
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| | Mogk, Axel [VerfasserIn] |
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| | Bukau, Bernd [VerfasserIn] |
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| | Nussbaum-Krammer, Carmen [VerfasserIn] |
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| Titel: | Disassembly of Tau fibrils by the human Hsp70 disaggregation machinery generates small seeding-competent species |
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| Verf.angabe: | Eliana Nachman, Anne S. Wentink, Karine Madiona, Luc Bousset, Taxiarchis Katsinelos, Kieren Allinson, Harm Kampinga, William A. McEwan, Thomas R. Jahn, Ronald Melki, Axel Mogk, Bernd Bukau, and Carmen Nussbaum-Krammer |
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| E-Jahr: | 2020 |
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| Jahr: | May 28, 2020 |
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| Umfang: | 15 S. |
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| Fussnoten: | Gesehen am 28.10.2020 |
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| Titel Quelle: | Enthalten in: JBC papers in press |
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| Ort Quelle: | Bethesda, MD. : American Soc. for Biochemistry and Molecular Biology, 2003 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 295(2020), 28, Seite 9676-9690 |
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| ISSN Quelle: | 1083-351X |
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| Abstract: | The accumulation of amyloid Tau aggregates is implicated in Alzheimer's disease (AD) and other tauopathies. Molecular chaperones are known to maintain protein homeostasis. Here, we show that an ATP-dependent human chaperone system disassembles Tau fibrils in vitro. We found that this function is mediated by the core chaperone HSC70, assisted by specific cochaperones, in particular class B J-domain proteins and a heat shock protein 110 (Hsp110)-type nucleotide exchange factor (NEF). The Hsp70 disaggregation machinery processed recombinant fibrils assembled from all six Tau isoforms as well as Sarkosyl-resistant Tau aggregates extracted from cell cultures and human AD brain tissues, demonstrating the ability of the Hsp70 machinery to recognize a broad range of Tau aggregates. However, the chaperone activity released monomeric and small oligomeric Tau species, which induced the aggregation of self-propagating Tau conformers in a Tau cell culture model. We conclude that the activity of the Hsp70 disaggregation machinery is a double-edged sword, as it eliminates Tau amyloids at the cost of generating new seeds. |
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| DOI: | doi:10.1074/jbc.RA120.013478 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1074/jbc.RA120.013478 |
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| | Volltext: http://www.jbc.org/content/295/28/9676 |
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| | DOI: https://doi.org/10.1074/jbc.RA120.013478 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | 70-kilodalton heat shock protein (Hsp70) |
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| | amyloid |
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| | chaperone DnaJ (DnaJ) |
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| | chaperone DNAJ (DNAJ) |
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| | molecular chaperone |
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| | neurodegenerative disease |
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| | prion |
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| | protein aggregation |
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| | proteostasis |
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| | Tau |
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| | Tau protein |
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| | tauopathy |
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| K10plus-PPN: | 1736848445 |
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| Verknüpfungen: | → Zeitschrift |
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Disassembly of Tau fibrils by the human Hsp70 disaggregation machinery generates small seeding-competent species / Nachman, Eliana [VerfasserIn]; May 28, 2020 (Online-Ressource)
