Heterotypic Aβ interactions facilitate amyloid assembly and modify amyloid structure
Heterotypic Aβ interactions facilitate amyloid assembly and modify amyloid structure
Abstract It is still unclear why pathological amyloid deposition initiates in specific brain regions, nor why specific cells or tissues are more susceptible than others. Amyloid deposition is determined by the self-assembly of short protein segments called aggregation-prone regions (APRs) that favour cross-β structure. Here we investigated whether Aβ amyloid assembly can be modified by heterotypic interactions between Aβ APRs and short homologous segments in otherwise unrelated human proteins. We identified heterotypic interactions that accelerate Aβ assembly, modify fibril morphology and affect its pattern of deposition in vitro. Moreover, we found that co-expression of these proteins in an Aβ reporter cell line promotes Aβ amyloid aggregation. Importantly, reanalysis of proteomics data of Aβ plaques from AD patients revealed an enrichment in proteins that share homologous sequences to the Aβ APRs, suggesting heterotypic amyloid interactions may occur in patients. Strikingly, we did not find such a bias in plaques from overexpression models in mouse. Based on these data, we propose that heterotypic APR interactions may play a hitherto unrealised role in amyloid-deposition diseases.
Ramakers Meine、De Vleeschouwer Matthias、Ribeiro Lu¨as F.、de Wit Joris、Schymkowitz Joost、Rousseau Frederic、Konstantoulea Katerina、Houben Bert、Louros Nikolaos、Lampi Yulia、Guerreiro Patricia、Xue Wei-Feng、Michiels Emiel、Aubrey Liam
Switch Laboratory, VIB Center for Brain and Disease Research||Switch Laboratory, Department of Cellular and Molecular Medicine, KULeuvenSwitch Laboratory, VIB Center for Brain and Disease Research||Switch Laboratory, Department of Cellular and Molecular Medicine, KULeuvenVIB Center for Brain & Disease Research||KU Leuven, Department of Neurosciences, Leuven Brain InstituteVIB Center for Brain & Disease ResearchSwitch Laboratory, VIB Center for Brain and Disease Research||Switch Laboratory, Department of Cellular and Molecular Medicine, KULeuvenSwitch Laboratory, VIB Center for Brain and Disease Research||Switch Laboratory, Department of Cellular and Molecular Medicine, KULeuvenSwitch Laboratory, VIB Center for Brain and Disease Research||Switch Laboratory, Department of Cellular and Molecular Medicine, KULeuvenSwitch Laboratory, VIB Center for Brain and Disease Research||Switch Laboratory, Department of Cellular and Molecular Medicine, KULeuvenSwitch Laboratory, VIB Center for Brain and Disease Research||Switch Laboratory, Department of Cellular and Molecular Medicine, KULeuvenSwitch Laboratory, VIB Center for Brain and Disease Research||Switch Laboratory, Department of Cellular and Molecular Medicine, KULeuvenSwitch Laboratory, VIB Center for Brain and Disease Research||Switch Laboratory, Department of Cellular and Molecular Medicine, KULeuvenSchool of Biosciences, University of KentSwitch Laboratory, VIB Center for Brain and Disease Research||Switch Laboratory, Department of Cellular and Molecular Medicine, KULeuvenSchool of Biosciences, University of Kent
基础医学神经病学、精神病学分子生物学
Ramakers Meine,De Vleeschouwer Matthias,Ribeiro Lu¨as F.,de Wit Joris,Schymkowitz Joost,Rousseau Frederic,Konstantoulea Katerina,Houben Bert,Louros Nikolaos,Lampi Yulia,Guerreiro Patricia,Xue Wei-Feng,Michiels Emiel,Aubrey Liam.Heterotypic Aβ interactions facilitate amyloid assembly and modify amyloid structure[EB/OL].(2025-03-28)[2025-05-08].https://www.biorxiv.org/content/10.1101/2021.04.28.441786.点此复制
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