Glial Senescence and Neuroinflammatory Mechanisms in Tauopathies: From Cellular Pathways to Therapeutic Targets

Tauopathies are a group of neurodegenerative disorders characterized by the abnormal accumulation and propagation of pathological tau protein in the brain. Increasing evidence suggests that disease progression is driven not only by neuronal dysfunction but also by profound alterations in glial cell biology. Astrocytes, microglia, and oligodendrocytes respond to pathological tau by adopting reactive and senescent phenotypes that contribute to chronic neuroinflammation, impaired tissue homeostasis, and progressive neurodegeneration. The senescence-associated secretory phenotype (SASP) produced by dysfunctional glial cells may further amplify inflammatory signaling, exacerbate tau pathology, and disrupt neuronal function. Despite growing interest in these mechanisms, the molecular pathways linking pathological tau, glial senescence, and neuroinflammation remain incompletely understood. A deeper understanding of these interactions is essential to uncover novel biomarkers and therapeutic targets for tauopathies.This Research Topic aims to advance our understanding of the cellular and molecular mechanisms that drive glial senescence and neuroinflammatory responses in tauopathies. Despite growing evidence implicating senescent glial cells in disease progression, important questions remain regarding how pathological tau initiates and sustains glial dysfunction, how different glial populations contribute to disease heterogeneity, and how these pathways may be therapeutically targeted. We seek to bring together basic, translational, and clinical studies that investigate the interplay between tau pathology, glial biology, cellular senescence, and neuroinflammation. By integrating emerging findings from experimental models, human tissues, and multi-omics approaches, this collection will work to identify key pathogenic mechanisms, highlight novel biomarkers, and explore therapeutic strategies capable of restoring glial homeostasis and slowing neurodegenerative progression.We welcome Original Research, Reviews, Mini-Reviews, Perspectives, and Methods articles addressing, but not limited to, the following topics: • Molecular mechanisms of glial senescence;• Tau-induced dysfunction in astrocytes, microglia, and oligodendrocytes• SASP signaling• Neuroinflammatory pathways in tauopathies• Glial contributions to tau propagation and clearance• Biomarkers of glial senescence• Single-cell and spatial transcriptomic approaches• Interactions between aging and tau pathology• Therapeutic strategies including senolytics, senomorphics, and immunomodulatory approaches. Contributions investigating disease-specific tau species, glial heterogeneity, and translational applications in Alzheimer’s disease, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, and related tauopathies are particularly encouraged. Topic editors: FADHL AL-SHAEBI, Khalil Ali Ahmad, Nemil Bhatt, Anna Fracassi Source: https://www.frontiersin.org/research-topics/82418/glial-senescence-and-neuroinflammatory-mechanisms-in-tauopathies-from-cellular-pathways-to-therapeutic-targets