Examinando por Autor "Labayru, Garazi"

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    Altered tubulin detyrosination due to SVBP malfunction induces cytokinesis failure and senescence, underlying a complex hereditary spastic paraplegia
    (John Wiley and Sons Inc, 2025-01) Launay, Nathalie; Espinosa Alcantud, Maria Dolores; Verdura, Edgar; Fernández García de Eulate, Gorka; Ondaro Ezkurra, Jon; Iruzubieta Agudo, Pablo; Marsal Terés, María; Schlüter, Agatha; Ruiz Sales, Montserrat; Fourcade, Stèphane; Rodríguez-Palmero Seuma, Agustí; Zulaica, Miren; Sistiaga Berrondo, Andone; Labayru, Garazi; Loza-Alvarez, Pablo; Vaquero, Alejandro; López de Munain Arregui, Adolfo; Pujol, Aurora
    Senescence, marked by permanent cell cycle arrest may contribute to the decline in regenerative potential and neuronal function, thereby promoting neurodegenerative disorders. In this study, we employed whole exome sequencing to identify a previously unreported biallelic missense variant in SVBP (p.Leu49Pro) in six patients from three unrelated families. These affected individuals present with a complex hereditary spastic paraplegia (HSP), peripheral neuropathy, verbal apraxia, and intellectual disability, exhibiting a milder phenotype compared to patients with nonsense SVBP mutations described previously. Consistent with SVBP's primary role as a chaperone necessary for VASH-mediated tubulin detyrosination, both patient fibroblasts with the p.Leu49Pro mutation, and HeLa cells harboring an SVBP knockdown exhibit microtubule dynamic instability and alterations in pericentriolar material (PCM) component trafficking and centrosome cohesion. In patient fibroblasts, structural abnormalities in the centrosome trigger mitotic errors and cellular senescence. Notably, premature senescence characterized by elevated levels of p16INK4, was also observed in patient peripheral blood mononuclear cells (PBMCs). Taken together, our findings underscore the critical role of SVBP in the development and maintenance of the central nervous system, providing novel insights associating cytokinesis failure with cortical motor neuron disease and intellectual disability.
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    Ítem
    Neural damage and inflammation in myotonic dystrophy type 1: longitudinal analysis of serum NFL, GFAP, and IL-6
    (Elsevier Inc., 2026-01) Garmendia, Joana; Labayru, Garazi ; Alberro, Ainhoa; Martins-Almeida, Laura; Otaegui Bichot, David; Iruzubieta Agudo, Pablo ; López de Munain Arregui, Adolfo; Sistiaga Berrondo, Andone
    Introduction: Myotonic dystrophy type 1 (DM1) is a progressive, multisystemic disease affecting the central nervous system (CNS). Blood-based biomarkers such as neurofilament light chain (NFL), glial fibrillary acidic protein (GFAP), and interleukin-6 (IL-6) offer potential as non-invasive indicators of CNS dysfunction and/or inflammation. However, their longitudinal dynamics and clinical relevance in DM1 remain unclear. Additionally, sex-related differences in these biomarkers are poorly understood. This study aimed to investigate NFL, GFAP, and IL-6 serum levels in patients with DM1, examine sex-differences, track changes over four years, and explore associations with genetic, muscular, cognitive, and neuroimaging outcomes. Method: Retrospective data from 70 DM1 patients and 54 healthy controls (HC) were analyzed. Longitudinal data were available for 68 participants (39 DM1, 29 HC). Biomarkers were measured using the ELLA immunoassay. DM1 patients had data on genetic, muscular, cognitive and structural brain outcomes. Analyses were adjusted for age. Results: NFL and IL-6 levels were significantly higher in DM1 patients compared to HC, while GFAP levels did not differ. Male DM1 patients exhibited higher NFL and IL-6 levels compared to females. No significant longitudinal changes were observed over a four-year period. NFL and IL-6 levels correlated with larger genetic expansions and poorer cognitive performance. Discussion: NFL and IL-6 may reflect neural damage and systemic inflammation in DM1 and could serve as biomarkers of cognitive dysfunction. However, their limited longitudinal sensitivity suggests longer follow-up is needed to evaluate their utility for disease monitoring.