dc.contributor.author | Asadzadeh, Jamshid | |
dc.contributor.author | Ruchti, Evelyne | |
dc.contributor.author | Jiao, Wei | |
dc.contributor.author | Limoni, Greta | |
dc.contributor.author | MacLachlan, Catherine | |
dc.contributor.author | Small, Scott A. | |
dc.contributor.author | Knott, Graham | |
dc.contributor.author | Santa-María, Ismael | |
dc.contributor.author | McCabe, Brian D. | |
dc.date.accessioned | 2023-04-04T09:06:12Z | |
dc.date.available | 2023-04-04T09:06:12Z | |
dc.date.issued | 2022 | |
dc.identifier.issn | 2041-1723 | spa |
dc.identifier.uri | https://hdl.handle.net/10641/3330 | |
dc.description.abstract | Alteration of the levels, localization or post-translational processing of the microtubule associated protein Tau is associated with many neurodegenerative disorders. Here we develop adult-onset models for human Tau (hTau) toxicity in Drosophila that enable age-dependent quantitative measurement of central nervous system synapse loss and axonal degeneration, in addition to effects upon lifespan, to facilitate evaluation of factors that may contribute to Tau-dependent neurodegeneration. Using these models, we interrogate the interaction of hTau with the retromer complex, an evolutionarily conserved cargo-sorting protein assembly, whose reduced activity has been associated with both Parkinson’s and late onset Alzheimer’s disease. We reveal that reduction of retromer activity induces a potent enhancement of hTau toxicity upon synapse loss, axon retraction and lifespan through a specific increase in the production of a C-terminal truncated isoform of hTau. Our data establish a molecular and subcellular mechanism necessary and sufficient for the depletion of retromer activity to exacerbate Tau-dependent neurodegeneration. | spa |
dc.language.iso | eng | spa |
dc.publisher | Nature Communications volume | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.title | Retromer deficiency in Tauopathy models enhances the truncation and toxicity of Tau. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dc.rights.accessRights | open access | spa |
dc.description.extent | 2287 KB | spa |
dc.identifier.doi | 10.1038/s41467-022-32683-5 | spa |
dc.relation.publisherversion | https://www.nature.com/articles/s41467-022-32683-5 | spa |