2026-04-13T04:50:52Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4859122025-08-31T18:26:38Zcom_2072_98col_2072_378192

2025-08-31T18:26:38Z urn:hdl:2072/485912 Exogenous prion-like proteins and their potential to trigger cognitive dysfunction Seira Curto, Jofre Dominguez-Martinez, Adán Perez Collell, Genis Barniol Simon, Estrella Romero Ruiz, Marina Franco Bordés, Berta Sotillo Sotillo, Paula Villegas Hernández, Sandra Fernández Gallegos, María Rosario Sánchez de Groot, Natalia Aggregation Amyloid Microbiome Neurodegeneration Prion Protein Altres ajuts: μFTIR experiments were performed at MIRAS beamline at ALBA Synchrotron with the collaboration of ALBA staff. Transmission electron microscopy (TEM) images were acquiredat the Servei de Microscòpia i Difracció de Raigs X (SMiDRX) of the Universitat Autònoma de Barcelona (UAB). The gut is exposed to a wide range of proteins, including ingested proteins and those produced by the resident microbiota. While ingested prion-like proteins can propagate across species, their implications for disease development remain largely unknown. Here, we apply a multidisciplinary approach to examine the relationship between the biophysical properties of exogenous prion-like proteins and the phenotypic consequences of ingesting them. Through computational analysis of gut bacterial proteins, we identified an enrichment of prion-like sequences in Helicobacter pylori. Based on these findings, we rationally designed a set of synthetic prion-like sequences that form amyloid fibrils, interfere with amyloid-beta-peptide aggregation, and trigger prion propagation when introduced in the yeast Sup35 model. When C. elegans were fed bacteria expressing these prion-like proteins, they lost associative memory and exhibited increased lipid oxidation. These data suggest a link between memory impairment, the conformational state of aggregates, and oxidative stress. Overall, this work supports gut microbiota as a reservoir of exogenous prion-like sequences, especially H. pylori, and the gut as an entry point for molecules capable of triggering cognitive dysfunction. 2025-08-31T18:26:38Z 2025-08-31T18:26:38Z 2025 Article http://hdl.handle.net/2072/485912 Ministerio de Ciencia, Innovación y Universidades FPU21/03897 Agencia Estatal de Investigación CNS2023-14443 Agencia Estatal de Investigación PID2020-117454RA-I0 Agencia Estatal de Investigación RYC2019-026752-I Molecular systems biology ; (2025) open access Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. https://creativecommons.org/licenses/by/4.0/