Exogenous Amyloid Sequences : Their Role in Amyloid-Beta Heterotypic Aggregation
Seira Curto, Jofre (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Villegas Hernandez, Sandra (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Fernandez, Maria Rosario (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Sánchez de Groot, Natalia (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2025
Resum:	Protein aggregation is a complex process influenced by environmental conditions and interactions between multiple molecules, including those of exogenous origin. Although in vitro simulations of aggregation are crucial for advancing research, few studies explore cross-seeding as a repeating event, despite the potential for such events when proteins circulate through the body. Here, we investigated the impact of exogenous amyloid sequences derived from the gut microbiota on the heterotypic aggregation of Aβ peptides. We utilized ten 21-amino acid peptides derived from bacterial genomes, previously shown to interfere with Aβ40 aggregation and induce memory loss in Caenorhabditis elegans. Through consecutive cross-seeding assays with Aβ40 and Aβ42, we analyzed the effects of these peptides on aggregation kinetics and seed propagation. Our findings indicate that exogenous molecules can influence Aβ's aggregation process, altering the fibrils' properties. Based on this, we introduce the "Interaction History" concept, where prior interactions shape the aggregation and propagation of Aβ peptides. This work supports the idea that environmental factors, such as microbial amyloids, can contribute to the heterogeneity and progression of amyloid-related diseases. Our results highlight the need for therapeutic strategies targeting diverse amyloid configurations and underscore the importance of considering exogenous sequences as additional triggers in AD pathology.
Ajuts:	Ministerio de Ciencia e Innovación RYC2019-026752-I Ministerio de Ciencia, Innovación y Universidades CNS2023-144437 Agencia Estatal de Investigación PID2020-117454RA-I00
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Prepublicació ; recerca ; Versió de l'autor
Matèria:	Microbiome ; Alzheimer's ; Aggregation ; Amyloid

DOI: 10.1101/2025.01.24.634659

21 p, 14.4 MB

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