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dc.contributor.advisorGutiérrez-Pérez, Antonia 
dc.contributor.advisorMorales Loyola, Rodrigo
dc.contributor.authorGómez Gutiérrez, Rubén
dc.contributor.otherBiología Celular, Genética y Fisiologíaes_ES
dc.date.accessioned2022-06-10T11:10:08Z
dc.date.available2022-06-10T11:10:08Z
dc.date.created2022-06-10
dc.date.issued2022
dc.date.submitted2022-01-26
dc.identifier.urihttps://hdl.handle.net/10630/24343
dc.descriptionSince BFA had the ability to cross-seed the aggregation of Aβ the gut commensal bacteria dysregulation could be a novel AD pathogenic mechanism and a potential therapeutic target.es_ES
dc.description.abstractAccumulation of amyloid-beta (Aβ) fibrils in the brain is associated with Alzheimer’s disease (AD) pathology. These fibrils exhibit distinct conformations or “strains” as consequence of variations in their molecular structure. Moreover, the amyloid structure of proteins has also been associated to important physiological functions, rising the term of functional amyloids. In bacteria these functional amyloids (BFA) are involved in biofilm formation, hence supporting bacterial adhesion, and antimicrobials and cytotoxic activities. Given the heterogeneity of AD and the increasing evidence that bacteria could be involved in AD, this thesis aimed to analyze the in vivo propagation of two different synthetic Aβ1-40 strains (2F and 3F) and the possibility that BFA cross-seed the in vitro and in vivo aggregation of Aβ. 2F and 3F fibrils were characterized by TEM, protease resistance, in vitro aggregation assays and LCOs and BFA (CsgA, microcin E492 and TasA) cross-seeding with Aβ was investigated by in vitro aggregation. To analyze the in vivo propagation, fibrils from all these proteins were intracerebrally administered in 50 days old Tg2576 mice. Prion-like transmission was assessed 250-days post-administration by immunolabeling and ELISA. Results showed that 2F and 3F fibrils induced the formation of Aβ aggregates with distinct brain tropism and unique structural morphologies, resulting in differential glial responses. The three BFA induced the aggregation of Aβ in vitro. However, only CsgA had the ability to cross-seed the in vivo aggregation of Aβ, with all BFA inducing Aβ aggregation with an incomplete attack rate. In conclusion, the distinct Aβ fibrils induced brain amyloidosis and inflammation in vivo, thus raising the possibility that different amyloid conformers might drive the heterogeneity found in AD patients.es_ES
dc.language.isoenges_ES
dc.publisherUMA Editoriales_ES
dc.rightsinfo:eu-repo/semantics/embargoedAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectUniversidad de Málaga - Tesis doctoraleses_ES
dc.subjectAlzheimer, Enfermedad dees_ES
dc.subjectPéptidoses_ES
dc.subjectProteinases_ES
dc.subject.otherAlzheimer'ses_ES
dc.subject.otherAmyloid-betaes_ES
dc.subject.otherStrainses_ES
dc.subject.otherCross-seedinges_ES
dc.titleConformational Aβ strains and cross-seeding mechanism in Alzheimer’s disease pathogenesis: In vivo studies in transgenic animal modelses_ES
dc.typeinfo:eu-repo/semantics/doctoralThesises_ES
dc.centroFacultad de Cienciases_ES
dc.rights.ccAttribution-NonCommercial-NoDerivatives 4.0 Internacional*


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