2026-04-13T08:15:45Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1962402025-12-04T19:01:36Zcom_2072_1057col_2072_478777col_2072_478916col_2072_478902col_2072_478917

00925njm 22002777a 4500 dc Ferrer, Isidro (Ferrer Abizanda) author Andrés Benito, Pol author Ausín, Karina author Cartas Cejudo, Paz author Lachén Montes, Mercedes author Río Fernández, José Antonio del author Fernández Irigoyen, Joaquín author Santamaría, Enrique author 2023-03-30T07:22:58Z 2023-07-15T05:10:26Z 2022-07-15 2023-03-30T07:22:58Z The neocortex of P301S mice, used as a model of fronto-temporal lobar degeneration linked to tau mutation (FTLD-tau), and wild-type mice, both aged 9 months, were analyzed with conventional label-free phosphoproteomics and SWATH-MS (sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) to assess the (phospho)proteomes. The total number of identified dysregulated phosphoproteins was 328 corresponding to 524 phosphorylation sites. The majority of dysregulated phosphoproteins, most of them hyperphosphorylated, were proteins of the membranes, synapses, membrane trafficking, membrane vesicles linked to endo- and exocytosis, cytoplasmic vesicles, and cytoskeleton. Another group was composed of kinases. In contrast, proteins linked to DNA, RNA metabolism, RNA splicing, and protein synthesis were hypophosphorylated. Other pathways modulating energy metabolism, cell signaling, Golgi apparatus, carbohydrates, and lipids are also targets of dysregulated protein phosphorylation in P301S mice. The present results, together with accompanying immunohistochemical and Western-blotting studies, show widespread abnormal phosphorylation of proteins, in addition to protein tau, in P301S mice. These observations point to dysregulated protein phosphorylation as a relevant contributory pathogenic component of tauopathies. Proteòmica Citosquelet Proteïnes quinases Proteomics Cytoskeleton Protein kinases Dysregulated Protein Phosphorylation in a Mouse Model of FTLD-Tau