Ptprd deficiency promotes tau hyperphosphorylation and impairs cognitive function in aged mice

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dc.article.number26
dc.catalogadorpva
dc.contributor.authorFoncea, Analía
dc.contributor.authorFranchini, Nayhara
dc.contributor.authorTobar, Isidora
dc.contributor.authorThienel, Sebastián
dc.contributor.authorRetamal, Ignacio N.
dc.contributor.authorCancino Lobos, Gonzalo
dc.contributor.authorCornejo, Francisca
dc.date.accessioned2025-05-16T17:11:02Z
dc.date.available2025-05-16T17:11:02Z
dc.date.issued2025
dc.date.updated2025-05-11T00:04:27Z
dc.description.abstractBackground Tau phosphorylation is a tightly regulated process that ensures proper neuronal function. Indeed, hyperphosphorylation of tau closely contributes to neuronal dysfunction leading to neurodegenerative diseases, including tauopathies, which are characterized by excessive and aberrant tau phosphorylation and cognitive decline. Therefore, it is important to understand how to regulate its phosphorylation. In this regard, the protein tyrosine phosphatase receptor delta (PTPRD) has been genetically implicated in tau pathology in humans, but the mechanisms underlying its role in tau regulation remain unclear. This study investigates the impact of Ptprd deficiency on tau phosphorylation, cognitive function, neuroinflammation, and synaptic markers in aging mice. Results Mice lacking Ptprd showed increased tau phosphorylation at multiple sites associated with its pathological aggregation. This effect was accompanied by the activation of the tau-related kinase Abl1, particularly in the hippocampus. Behavioral assessments revealed significant impairments in learning and memory, demonstrating the functional impact of these alterations. Moreover, Ptprd knockout mice showed increased microgliosis in both the entorhinal cortex and the hippocampus, suggesting a pro-inflammatory response. Furthermore, the synaptic protein PSD95 was also reduced in the cortex, indicating potential synaptic dysfunction. Conclusions The loss of Ptprd leads to increased tau phosphorylation, cognitive impairments, microgliosis, and synaptic alterations in older mice. Our findings also suggest that Ptprd plays a critical role in maintaining tau homeostasis through the Abl1 kinase. This indicates a new potential therapeutic approach for tauopathies, where PTPRD could serve a protective role against tau-related pathologies and may act as a key modulator in disease progression.
dc.fechaingreso.objetodigital2025-05-11
dc.format.extent12 páginas
dc.fuente.origenBiomed Central
dc.identifier.citationBiological Research. 2025 May 06;58(1):26
dc.identifier.doi10.1186/s40659-025-00607-4
dc.identifier.issn0717-6287
dc.identifier.urihttps://doi.org/10.1186/s40659-025-00607-4
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/104342
dc.information.autorucFacultad de Ciencias Biológicas; Cancino Lobos, Gonzalo; S/I; 17709
dc.issue.numero1
dc.language.isoen
dc.nota.accesocontenido completo
dc.publisherSpringer Nature
dc.revistaBiological Research
dc.rightsacceso abierto
dc.rights.holderThe Author(s)
dc.rights.licenseAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectPTPRD
dc.subjectTau phosphorylation
dc.subjectABL1
dc.subjectTauopathy
dc.subjectCognitive impairment
dc.subjectMicrogliosis
dc.subjectSynaptic dysfunction
dc.subject.ddc570
dc.subject.deweyBiologíaes_ES
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titlePtprd deficiency promotes tau hyperphosphorylation and impairs cognitive function in aged mice
dc.typeartículo
dc.volumen58
sipa.codpersvinculados17709
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