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Title: Tau Exon 10 inclusion by PrPC through downregulating GSK3β activity
Author: Lidón Gil, Laia
Llaó-Hierro, Laura
Nuvolone, Mario
Aguzzi, Adriano
Ávila, Jesús
Ferrer, Isidro (Ferrer Abizanda)
Río Fernández, José Antonio del
Gavín Marín, Rosalina
Keywords: Malalties neurodegeneratives
Malaltia d'Alzheimer
Neurodegenerative Diseases
Alzheimer's disease
Issue Date: 20-May-2021
Publisher: MDPI
Abstract: 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.
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It is part of: International Journal of Molecular Sciences, 2021, vol. 22, num. 10, p. 1-24
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ISSN: 1661-6596
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)

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