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Trans-seeding of Alzheimer-related tau protein by a yeast prion.
Flach, Martin; Leu, Cedric; Martinisi, Alfonso; Skachokova, Zhiva; Frank, Stephan; Tolnay, Markus; Stahlberg, Henning; Winkler, David T.
Afiliação
  • Flach M; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Leu C; Department of Neurology, University Hospital Basel, Basel, Switzerland.
  • Martinisi A; Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum, University of Basel, Basel, Switzerland.
  • Skachokova Z; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Frank S; Department of Neurology, University Hospital Basel, Basel, Switzerland.
  • Tolnay M; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Stahlberg H; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Winkler DT; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
Alzheimers Dement ; 18(12): 2481-2492, 2022 12.
Article em En | MEDLINE | ID: mdl-35142027
ABSTRACT
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."
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Príons / Tauopatias / Doença de Alzheimer Idioma: En Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Suíça

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Príons / Tauopatias / Doença de Alzheimer Idioma: En Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Suíça