Pyroptosis and Ferroptosis in Non-Neuronal Cells: Triggers and Propagation of Neuroinflammation in Aging

Research in neuroinflammation has increasingly highlighted the role of non-neuronal cells, such as microglia, astrocytes, oligodendrocytes, endothelial cells, and infiltrating immune cells, in shaping neural environments during aging and neurodegenerative diseases. Among the diverse mechanisms underlying glial and peripheral immune cell activity, recently characterized forms of regulated cell death, pyroptosis and ferroptosis, have attracted significant attention. Pyroptosis, a pro-inflammatory, gasdermin-mediated process, and ferroptosis, driven by iron-dependent lipid peroxidation, both induce cellular demise accompanied by the release of DAMPs and pro-inflammatory factors. Emerging evidence suggests that these distinct cell death pathways in non-neuronal populations can profoundly influence the initiation and propagation of neuroinflammatory cascades, which in turn impact synaptic function, neuronal survival, and cognitive resilience. Despite this progress, the precise triggers, regulatory networks, and in vivo relevance of pyroptosis and ferroptosis in the aged brain and their contribution to chronic neuroinflammation remain only partially understood.This Research Topic aims to advance our understanding of how pyroptosis and ferroptosis within non-neuronal cells drive neuroinflammation during aging and in neurodegenerative contexts. We seek to uncover the external and internal triggers, intracellular signaling mechanisms, and crosstalk events that orchestrate these cell death processes. Key objectives include identifying how such pathways modulate the neuroimmune landscape, delineating interactions between resident glial populations and infiltrating immune cells and assessing the therapeutic potential of targeting pyroptosis or ferroptosis to improve neuroinflammatory and neurodegenerative outcomes. By fostering a multidisciplinary dialogue, this collection strives to bridge basic mechanistic insights with translational and pharmacological research perspectives.To gather further insights into the impact of regulated cell death in non-neuronal cells on neuroinflammation and aging, we welcome articles addressing, but not limited to, the following themes:• Molecular triggers and upstream regulators of pyroptosis and ferroptosis in glial and peripheral immune cells• Interplay between oxidative stress, lipid peroxidation, and iron homeostasis in aging-related neuroinflammation• Cellular and molecular mechanisms dictating DAMP release and inflammatory signaling propagation by non-neuronal cell death• Reciprocal influences among astrocytes, microglia, oligodendrocytes, and endothelial cells via cell death pathways• The contribution of pyroptosis and ferroptosis to blood-brain barrier dysfunction, leukocyte infiltration, and neurovascular inflammation in aging• Experimental models and imaging modalities to dissect in vivo cell death processes in the aging brain• Pharmacological or genetic interventions targeting pyroptosis, ferroptosis, or their mediators to modulate neuroinflammatory and neurodegenerative phenotypesWe encourage a wide range of submissions, including original research, methods papers, brief research reports, data reports, systematic reviews, mini reviews and perspectives. Topic editors: Saleha Anwar, Marina Mejias Ortega Source: https://www.frontiersin.org/research-topics/76580/pyroptosis-and-ferroptosis-in-non-neuronal-cells-triggers-and-propagation-of-neuroinflammation-in-aging