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| Verfasst von: | Tittelmeier, Jessica [VerfasserIn]  |
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| | Sandhof, Carl Alexander [VerfasserIn] |
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| | Ries, Heidrun Maja [VerfasserIn] |
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| | Druffel-Augustin, Silke [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: | The HSP110/HSP70 disaggregation system generates spreading-competent toxic alpha-synuclein species |
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| Verf.angabe: | Jessica Tittelmeier, Carl Alexander Sandhof, Heidrun Maja Ries, Silke Druffel-Augustin, Axel Mogk, Bernd Bukau & Carmen Nussbaum-Krammer |
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| E-Jahr: | 2020 |
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| Jahr: | 25 May 2020 |
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| Umfang: | 16 S. |
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| Fussnoten: | Gesehen am 30.07.2020 |
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| Titel Quelle: | Enthalten in: European Molecular Biology OrganizationThe EMBO journal |
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| Ort Quelle: | Heidelberg : EMBO Press, 1982 |
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| Jahr Quelle: | 2020 |
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| Band/Heft Quelle: | 39(2020,13) Artikel-Nummer e103954, 16 Seiten |
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| ISSN Quelle: | 1460-2075 |
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| Abstract: | The accumulation and prion-like propagation of alpha-synuclein and other amyloidogenic proteins are associated with devastating neurodegenerative diseases. Metazoan heat shock protein HSP70 and its co-chaperones DNAJB1 and HSP110 constitute a disaggregation machinery that is able to disassemble alpha-synuclein fibrilsin vitro, but its physiological effects on alpha-synuclein toxicity are unknown. Here, we depletedCaenorhabditis elegansHSP-110 and monitored the consequences on alpha-synuclein-related pathological phenotypes such as misfolding, intercellular spreading, and toxicity inC. elegans in vivomodels. Depletion of HSP-110 impaired HSP70 disaggregation activity, prevented resolubilization of amorphous aggregates, and compromised the overall cellular folding capacity. At the same time, HSP-110 depletion reduced alpha-synuclein foci formation, cell-to-cell transmission, and toxicity. These data demonstrate that the HSP70 disaggregation activity constitutes a double-edged sword, as it is essential for maintaining cellular proteostasis but also involved in the generation of toxic amyloid-type protein species. |
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| DOI: | doi:10.15252/embj.2019103954 |
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| URL: | kostenfrei: Volltext: https://doi.org/10.15252/embj.2019103954 |
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| | DOI: https://doi.org/10.15252/embj.2019103954 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | aggregation |
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| | chaperone |
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| | chaperones |
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| | expression |
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| | hsp70 |
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| | in-vivo |
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| | mechanism |
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| | neurodegenerative diseases |
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| | polyglutamine-expansion |
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| | prion protein |
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| | prion-like propagation |
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| | propagation |
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| | protein disaggregation |
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| | protein disaggregation |
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| | proteostasis |
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| K10plus-PPN: | 1725942100 |
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| Verknüpfungen: | → Zeitschrift |
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| Lokale URL UB: |  Zum Volltext |
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¬The¬ HSP110/HSP70 disaggregation system generates spreading-competent toxic alpha-synuclein species / Tittelmeier, Jessica [VerfasserIn]; 25 May 2020 (Online-Ressource)
