2026-04-13T05:44:33Zhttps://recercat.cat/oai/request

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

00925njm 22002777a 4500 dc Seira Curto, Jofre author Dominguez-Martinez, Adán author Perez Collell, Genis author Barniol Simon, Estrella author Romero Ruiz, Marina author Franco Bordés, Berta author Sotillo Sotillo, Paula author Villegas Hernández, Sandra author Fernández Gallegos, María Rosario author Sánchez de Groot, Natalia author 2025 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. http://hdl.handle.net/2072/485912 Aggregation Amyloid Microbiome Neurodegeneration Prion Protein Exogenous prion-like proteins and their potential to trigger cognitive dysfunction