Cell Death Modalities in Neurological Disorders: Mechanisms, Crosstalk, and Translational Perspectives

Cell death research has emerged as a cornerstone for understanding the pathogenesis of neurological disorders. Neurons and glial cells in the central nervous system are continually exposed to metabolic, oxidative, and inflammatory stressors, making them especially vulnerable to dysregulation in cell death pathways. Historically, apoptosis was viewed as the primary driver of programmed cell loss in neurodegenerative diseases. However, accumulating evidence demonstrates that this perspective is incomplete, with diverse regulated cell death modalities such as pyroptosis, ferroptosis, cuproptosis, disulfidptosis, necroptosis, and PANoptosis playing critical, context-dependent roles. Each of these pathways involves unique molecular machinery, metabolic dependencies, and tissue-specific manifestations, yet often display intricate crosstalk and compensatory interactions within the landscape of CNS pathology. Recent multi-omics studies and advanced imaging techniques have revealed the coexistence of multiple cell death programs—and the modulatory influence of neuroinflammatory processes—in neurodegenerative diseases and acute brain injuries. Despite these advances, decisive gaps persist regarding the spatiotemporal regulation of these pathways, the interplay among affected cell types, and the identification of reliable, translational biomarkers distinguishing specific death signatures.This Research Topic aims to synthesize and advance understanding of the diversity and complexity of regulated cell death modalities in neurological disorders. Central objectives include delineating the molecular and metabolic mechanisms guiding apoptosis, pyroptosis, ferroptosis, cuproptosis, disulfidptosis, necroptosis, and PANoptosis within disease-relevant contexts; clarifying how these pathways integrate and crosstalk at both cellular and tissue levels; and exploring the translational implications for therapeutic intervention. Particular attention is directed toward the dynamic roles of cell type specificity (neurons, astrocytes, microglia, oligodendrocytes, endothelial cells), disease staging, and interactions with neuroinflammation. This Research Topic also seeks to inspire approaches utilizing multi-omics profiling, innovative disease models, and next-generation imaging to identify actionable biomarkers and new therapeutic windows.To stimulate comprehensive exploration while maintaining focus, this Research Topic is limited to the mechanistic, regulatory, and translational aspects of regulated cell death pathways in neurological disorders, with an emphasis on integrative perspectives and actionable insights. We welcome articles addressing, but not limited to, the following themes:- Molecular mechanisms and disease relevance of apoptosis, pyroptosis, ferroptosis, cuproptosis, disulfidptosis, necroptosis, and PANoptosis- Crosstalk and integrated regulatory circuits among cell death pathways- Cell type–specific regulation and consequences in neurons, glia, and vascular cells- Links between metal ion homeostasis, lipid metabolism, redox status, and cell death- Mitochondrial dysfunction and metabolic reprogramming as upstream regulators- Bidirectional influences between programmed cell death and neuroinflammation- Strategies for multi-omics–based biomarker discovery and disease monitoring- Pharmacological targeting of cell death pathways: preclinical and clinical insights- Temporal mapping of cell death activation and therapeutic response opportunities Topic editors: Rui Duan, Mingkuan Sun, Jiefu Jin Source: https://www.frontiersin.org/research-topics/79464/cell-death-modalities-in-neurological-disorders-mechanisms-crosstalk-and-translational-perspectives