Percorrer por autor "Dias, Daniela Carina Oliveira"
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- Phosphoproteomic signature of the microglial cytoskeleton of the 5xFAD model of Alzheimer´sPublication . Dias, Daniela Carina Oliveira; Socodato, Renato; Portugal, Camila C.; Ferraz, RicardoAlzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the extracellular deposition of β -amyloid peptides (Aβ) and the accumulation of hyperphosphorylated tau proteins, leading to cognitive and neuronal dysfunction. The cytoskeleton, a complex and dynamic structure, is crucial for the organization and morphology of microglia, supporting their motility, phagocytosis, and immune surveillance in the CNS. This study employs proteomic and phosphoproteomic approaches to investigate site-specific phosphorylation changes that are representative of structural and functional changes in the microglial cytoskeleton in response to AD. The bioinformatics analysis carried out allowed the identification of critical cellular components such as actin cytoskeleton and microtubule cytoskeleton, both essential for microglia to respond to pathological stimuli. We identified a total of 131 differentially abundant phosphopeptides between WT and 5xFAD. Among them, a key outcome was the hyperphosphorylation of Septin2 at residue S218, which showed an approximately 2.5-fold increase in 5xFAD compared to WT (q-value = 3.5e10-4). Alterations in the dynamics of these cellular components destabilize the organization and behavior of the microglial cytoskeleton, contributing to the progression of pathology in the 5xFAD murine model. Notably, increased levels of Septin phosphorylation, essential regulators of cytoskeletal dynamics, were observed. These findings suggest that dysfunctions in the microglial cytoskeleton create an environment conducive to the initiation of neurodegenerative cascades in Alzheimer's disease.