Trans‐seeding of Alzheimer‐related tau protein by a yeast prion
| Autor: | Martin Flach, Cedric Leu, Alfonso Martinisi, Zhiva Skachokova, Stephan Frank, Markus Tolnay, Henning Stahlberg, David T. Winkler |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Alzheimer's & Dementia. 18:2481-2492 |
| ISSN: | 1552-5279 1552-5260 |
| DOI: | 10.1002/alz.12581 |
| Popis: | Abnormal tau protein aggregates constitute a hallmark of Alzheimer's disease. The mechanisms underlying the initiation of tau aggregation in sporadic neurodegeneration remain unclear. Here we investigate whether a non-human prion can seed tau aggregation. Due to their structural similarity with tau aggregates, we chose Sup35NM yeast prion domain fibrils for explorative tau seedings. Upon in vitro incubation with tau monomers, Sup35NM fibrils promoted the formation of morphologically distinct tau fibril strains. In vivo, intrahippocampal inoculation of Sup35NM fibrils accentuated tau pathology in P301S tau transgenic mice. Thus, our results provide first in vivo evidence for heterotypic cross-species seeding of a neurodegenerative human prion-like protein by a yeast prion. This opens up the conceptual perspective that non-mammalian prions present in the human microbiome could be involved in the initiation of protein misfolding in neurodegenerative disorders, a mechanism for which we propose the term "trans-seeding." |
| Databáze: | OpenAIRE |
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