دورية أكاديمية
The HSP40 chaperone Ydj1 drives amyloid beta 42 toxicity
| العنوان: | The HSP40 chaperone Ydj1 drives amyloid beta 42 toxicity |
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| المؤلفون: | Julia Ring, Jelena Tadic, Selena Ristic, Michael Poglitsch, Martina Bergmann, Nemanja Radic, Dirk Mossmann, YongTian Liang, Marta Maglione, Andrea Jerkovic, Roozbeh Hajiraissi, Marcel Hanke, Victoria Küttner, Heimo Wolinski, Andreas Zimmermann, Lana Domuz Trifunović, Leonie Mikolasch, Daiana N Moretti, Filomena Broeskamp, Julia Westermayer, Claudia Abraham, Simon Schauer, Christopher Dammbrueck, Sebastian J Hofer, Mahmoud Abdellatif, Guido Grundmeier, Guido Kroemer, Ralf J Braun, Niklas Hansen, Cornelia Sommer, Mirjana Ninkovic, Sandra Seba, Patrick Rockenfeller, Friederike‐Nora Vögtle, Jörn Dengjel, Chris Meisinger, Adrian Keller, Stephan J Sigrist, Tobias Eisenberg, Frank Madeo |
| المصدر: | EMBO Molecular Medicine, Vol 14, Iss 5, Pp n/a-n/a (2022) |
| بيانات النشر: | Springer Nature, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Medicine (General) LCC:Genetics |
| مصطلحات موضوعية: | Alzheimer’s disease, amyloid beta 42, heat shock proteins, HSP40, oligomers, Medicine (General), R5-920, Genetics, QH426-470 |
| الوصف: | Abstract Amyloid beta 42 (Abeta42) is the principal trigger of neurodegeneration during Alzheimer’s disease (AD). However, the etiology of its noxious cellular effects remains elusive. In a combinatory genetic and proteomic approach using a yeast model to study aspects of intracellular Abeta42 toxicity, we here identify the HSP40 family member Ydj1, the yeast orthologue of human DnaJA1, as a crucial factor in Abeta42‐mediated cell death. We demonstrate that Ydj1/DnaJA1 physically interacts with Abeta42 (in yeast and mouse), stabilizes Abeta42 oligomers, and mediates their translocation to mitochondria. Consequently, deletion of YDJ1 strongly reduces co‐purification of Abeta42 with mitochondria and prevents Abeta42‐induced mitochondria‐dependent cell death. Consistently, purified DnaJ chaperone delays Abeta42 fibrillization in vitro, and heterologous expression of human DnaJA1 induces formation of Abeta42 oligomers and their deleterious translocation to mitochondria in vivo. Finally, downregulation of the Ydj1 fly homologue, Droj2, improves stress resistance, mitochondrial morphology, and memory performance in a Drosophila melanogaster AD model. These data reveal an unexpected and detrimental role for specific HSP40s in promoting hallmarks of Abeta42 toxicity. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1757-4684 1757-4676 |
| Relation: | https://doaj.org/toc/1757-4676; https://doaj.org/toc/1757-4684 |
| DOI: | 10.15252/emmm.202113952 |
| URL الوصول: | https://doaj.org/article/4c65d2eea54842d29ae6240b593bf7ff |
| رقم الأكسشن: | edsdoj.4c65d2eea54842d29ae6240b593bf7ff |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 17574684 17574676 |
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| DOI: | 10.15252/emmm.202113952 |