Examinando por Autor "Lersundi Artamendi, Ana"

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    Ítem
    Dysregulated FOXO1 activity drives skeletal muscle intrinsic dysfunction in amyotrophic lateral sclerosis
    (Springer Science and Business Media Deutschland GmbH, 2024-09-16) Zufiría García, Mónica; Pikatza-Menoio, Oihane; Garciandia Arcelus, Maddi; Bengoetxea Bausela, Xabier; Jiménez Zúñiga, Andrés; Elicegui, Amaia; Levchuk, María; Arnold García, Olatz; Ondaro Ezkurra, Jon; Iruzubieta Agudo, Pablo; Rodríguez Gómez, Laura; Fernández Pelayo, Uxoa; Muñoz Oreja, Mikel; Aiastui Pujana, Ana; García Verdugo, Jose Manuel; Herranz Pérez, Vicente; Zulaica, Miren; Poza Aldea, Juan José; Ruiz Onandi, Rebeca; Fernández Torrón, Roberto; Espinal Valencia, Juan Bautista; Bonilla Zagala, Mario; Lersundi Artamendi, Ana; Fernández-Eulate, Gorka; Riancho Zarrabeitia, Javier; Vallejo Illarramendi, Ainara; Holt, Ian James; Sáenz, Amets; Malfatti, Edoardo; Duguez, Stéphanie; Blázquez García, Lorea; López de Munain Arregui, Adolfo; Gereñu Lopetegi, Gorka; Gil Bea, Francisco Javier; Alonso-Martin, Sonia
    Amyotrophic Lateral Sclerosis (ALS) is a multisystemic neurodegenerative disorder, with accumulating evidence indicating metabolic disruptions in the skeletal muscle preceding disease symptoms, rather than them manifesting as a secondary consequence of motor neuron (MN) degeneration. Hence, energy homeostasis is deeply implicated in the complex physiopathology of ALS and skeletal muscle has emerged as a key therapeutic target. Here, we describe intrinsic abnormalities in ALS skeletal muscle, both in patient-derived muscle cells and in muscle cell lines with genetic knockdown of genes related to familial ALS, such as TARDBP (TDP-43) and FUS. We found a functional impairment of myogenesis that parallels defects of glucose oxidation in ALS muscle cells. We identified FOXO1 transcription factor as a key mediator of these metabolic and functional features in ALS muscle, via gene expression profiling and biochemical surveys in TDP-43 and FUS-silenced muscle progenitors. Strikingly, inhibition of FOXO1 mitigated the impaired myogenesis in both the genetically modified and the primary ALS myoblasts. In addition, specific in vivo conditional knockdown of TDP-43 or FUS orthologs (TBPH or caz) in Drosophila muscle precursor cells resulted in decreased innervation and profound dysfunction of motor nerve terminals and neuromuscular synapses, accompanied by motor abnormalities and reduced lifespan. Remarkably, these phenotypes were partially corrected by foxo inhibition, bolstering the potential pharmacological management of muscle intrinsic abnormalities associated with ALS. The findings demonstrate an intrinsic muscle dysfunction in ALS, which can be modulated by targeting FOXO factors, paving the way for novel therapeutic approaches that focus on the skeletal muscle as complementary target tissue.
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    Ítem
    Manual therapy and neck-specific exercise are equally effective for treating non-specific neck pain but only when exercise adherence is maximised: a randomised controlled trial
    (Elsevier Ltd, 2025-03-21) Villanueva Ruiz, Iker; Falla, Deborah; Saez, Marc; Araolaza Arrieta, Maialen; Azkue Barrenetxea, Jon Jatsu; Arbillaga Etxarri, Ane; Lersundi Artamendi, Ana; Lascurain-Aguirrebeña, Ion
    Objective: To assess the effectiveness of manual therapy versus a progressive, tailored neck-specific exercise program with high adherence for treating non-specific chronic neck pain (NSNP) and to examine the relationship between exercise adherence and treatment outcome. Design: Single-blind, parallel, randomized clinical trial with two treatment arms, adhering to CONSORT guidelines. Methods: 65 NSNP participants were randomly allocated to manual therapy or exercise. They received four treatment sessions of either manual therapy or neck-specific exercise, once a week for four weeks. Outcomes measured at baseline, two weeks, four weeks, and 12 weeks post-treatment included pain intensity, disability, patient-perceived improvement, quality of life, kinesiophobia and the craniocervical flexion test (CCFT) performance. In addition to evaluating each individual outcome, patients were categorized into either responders or non-responders according to pain intensity, disability and patient-perceived improvement. Exercise adherence was recorded. Results: There were no differences between groups in individual outcomes. Treatment outcome in the exercise group was associated with exercise adherence. Patients receiving manual therapy were more likely to be classified as responders than those receiving exercise at all measured time points (odds ratio, 2 weeks: 0.14; 95 % CI: 0.02–0.79; treatment completion: 0.31; 95 % CI: 0.12–0.82; 12 weeks after treatment completion: 0.19; 95 % CI: 0.05–0.65), however these differences were no longer present when only patients whose exercise adherence was ≥95 % were analysed. Exercise was more effective than manual therapy in improving CCFT performance but only if patients with ≥95 % adherence were considered. Conclusion: A four-week intervention of manual therapy was more effective than exercise, however when exercise adherence was ≥95 %, the interventions were equally effective. Manual therapy may only be superior to specific-exercise when high exercise adherence cannot be assured.
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    Ítem
    The role of integrin β1D mislocalization in the pathophysiology of calpain 3-related limb–girdle muscular dystrophy
    (Multidisciplinary Digital Publishing Institute (MDPI), 2025-03) Valls Rodríguez, Andrea; Ruiz Roldán, Cristina; Immanuel, Jenita; Alonso-Martin, Sonia; Gallardo, Eduard; Fernández Torrón, Roberto; Bonilla Zagala, Mario; Lersundi Artamendi, Ana; Hernández Laín, A.; Domínguez González, Cristina; Vílchez, Juan J.; Iruzubieta Agudo, Pablo; López de Munain Arregui, Adolfo; Sáenz, Amets
    Limb–girdle muscular dystrophy R1 (LGMDR1) is characterized by progressive proximal muscle weakness due to mutations in the CAPN3 gene. Little is known about CAPN3’s function in muscle, but its loss results in aberrant sarcomere formation. Human muscle structure was analyzed in this study, with observations including integrin β1D isoform (ITGβ1D) mislocalization, a lack of Talin-1 (TLN1) in the sarcolemma and the irregular expression of focal adhesion kinase (FAK) in LGMDR1 muscles, suggesting a lack of integrin activation with an altered sarcolemma, extracellular matrix (ECM) assembly and signaling pathway deregulation, which may cause frailty in LGMDR1 muscle fibers. Additionally, altered nuclear morphology, centrosome distribution and microtubule organization have been found in muscle cells derived from LGMDR1 patients