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String/Cdc25 phosphatase is a suppressor of Tau-associated neurodegeneration

dc.contributor.authorOliveira, Andreia C.
dc.contributor.authorSantos, Madalena
dc.contributor.authorPinho, Mafalda
dc.contributor.authorLopes, Carla S.
dc.date.accessioned2026-01-15T14:39:57Z
dc.date.available2026-01-15T14:39:57Z
dc.date.issued2023-01-23
dc.description.abstractTau pathology is defined by the intracellular accumulation of abnormally phosphorylated Tau (MAPT) and is prevalent in several neurodegenerative disorders. The identification of modulators of Tau abnormal phosphorylation and aggregation is key to understanding disease progression and developing targeted therapeutic approaches. In this study, we identified String (Stg)/Cdc25 phosphatase as a suppressor of abnormal Tau phosphorylation and associated toxicity. Using a Drosophila model of tauopathy, we showed that Tau dephosphorylation by Stg/Cdc25 correlates with reduced Tau oligomerization, brain vacuolization and locomotor deficits in flies. Moreover, using a disease mimetic model, we provided evidence that Stg/Cdc25 reduces Tau phosphorylation levels independently of Tau aggregation status and delays neurodegeneration progression in the fly. These findings uncover a role for Stg/Cdc25 phosphatases as regulators of Tau biology that extends beyond their well-characterized function as cell-cycle regulators during cell proliferation, and indicate Stg/Cdc25-based approaches as promising entry points to target abnormal Tau phosphorylation.eng
dc.identifier.citationOliveira, A. C., Santos, M., Pinho, M., & Lopes, C. S. (2023). String/Cdc25 phosphatase is a suppressor of Tau-associated neurodegeneration. Disease Models & Mechanisms, 16(1), dmm049693. https://doi.org/10.1242/dmm.049693
dc.identifier.doi10.1242/dmm.049693
dc.identifier.eissn1754-8411
dc.identifier.issn1754-8403
dc.identifier.urihttp://hdl.handle.net/10400.22/31536
dc.language.isoeng
dc.peerreviewedyes
dc.publisherThe Company of Biologists Ltd
dc.relationPOCI- 01-0145-FEDER-007274; NORTE-01-0145-FEDER-000008; SFRH/BD/130119/2017
dc.relation.hasversionhttps://journals.biologists.com/dmm/article/16/1/dmm049693/286728/String-Cdc25-phosphatase-is-a-suppressor-of-Tau
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectTauopathy
dc.subjectStg/Cdc25
dc.subjectTau
dc.subjectDrosophila
dc.subjectNeurodegeneration
dc.titleString/Cdc25 phosphatase is a suppressor of Tau-associated neurodegenerationeng
dc.typeresearch article
dspace.entity.typePublication
oaire.citation.issue1
oaire.citation.titleDisease Models & Mechanisms
oaire.citation.volume16
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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