Carregant...
Fitxers
Tipus de document
ArticleVersió
Versió publicadaData de publicació
Llicència de publicació
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/180457
Tau Exon 10 inclusion by PrPC through downregulating GSK3β activity
Títol de la revista
Director/Tutor
ISSN de la revista
Títol del volum
Recurs relacionat
Resum
Tau protein is largely responsible for tauopathies, including Alzheimer's disease (AD),where it accumulates in the brain as insoluble aggregates. Tau mRNA is regulated by alternativesplicing, and inclusion or exclusion of exon 10 gives rise to the 3R and 4R isoforms respectively, whosebalance is physiologically regulated. In this sense, one of the several factors that regulate alternativesplicing of tau is GSK3β, whose activity is inhibited by the cellular prion protein (PrPC), whichhas different physiological functions in neuroprotection and neuronal differentiation. Moreover, arelationship between PrPCand tau expression levels has been reported during AD evolution. Forthis reason, in this study we aimed to analyze the role of PrPCand the implication of GSK3βin theregulation of tau exon 10 alternative splicing. We used AD human samples and mouse models ofPrPCablation and tau overexpression. In addition, we used primary neuronal cultures to developfunctional studies. Our results revealed a paralleled association between PrPCexpression and tau4R isoforms in all models analyzed. In this sense, reduction or ablation of PrPClevels induces anincrease in tau 3R/4R balance. More relevantly, our data points to GSK3βactivity downstream fromPrPCin this phenomenon. Our results indicate that PrPCplays a role in tau exon 10 inclusion throughthe inhibitory capacity of GSK3β.
Matèries (anglès)
Citació
Citació
LIDÓN GIL, Laia, LLAÓ-HIERRO, Laura, NUVOLONE, Mario, AGUZZI, Adriano, ÁVILA, Jesús, FERRER, Isidro (ferrer abizanda), RÍO FERNÁNDEZ, José antonio del, GAVÍN MARÍN, Rosalina. Tau Exon 10 inclusion by PrPC through downregulating GSK3β activity. _International Journal of Molecular Sciences_. 2021. Vol. 22, núm. 10, pàgs. 1-24. [consulta: 25 de gener de 2026]. ISSN: 1661-6596. [Disponible a: https://hdl.handle.net/2445/180457]