Beyond Apoptosis: Molecular Mechanisms of Regulated Cell Death in the Nervous System

Non-apoptotic regulated cell death pathways such as ferroptosis, pyroptosis, necroptosis, and parthanatos are increasingly recognized as major drivers of neuronal and glial loss across a broad spectrum of neurological conditions, including ischemic stroke, traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Each pathway is governed by distinct molecular signaling cascades: iron-dependent lipid peroxidation in ferroptosis, inflammasome-mediated gasdermin pore formation in pyroptosis, RIPK1/RIPK3/MLKL-driven membrane disruption in necroptosis, and PARP1 hyperactivation in parthanatos. These mechanisms frequently intersect with mitochondrial dysfunction, redox imbalance, and neuroinflammatory signaling, yet the cell-type specificity, developmental regulation, and crosstalk among these pathways in the nervous system remain poorly defined.This Research Topic aims to bring together studies that dissect the molecular machinery of non-apoptotic cell death in neural cells and that connect pathway-specific mechanisms to defined neuropathological outcomes. By integrating molecular, genetic, and pharmacological perspectives, this collection seeks to map the signaling networks that determine how and when neurons and glia engage specific death modalities, and to identify targetable nodes for therapeutic neuroprotection.We welcome contributions using biochemical, genetic, imaging, metabolomic, and multi-omic approaches, including work in genetically engineered animal models, human iPSC-derived neural systems, and organoids. Studies identifying pathway-selective biomarkers, small-molecule modulators, or gene-based strategies to block pathological cell death while preserving homeostatic functions are particularly encouraged.Dr. Matija Zelic is employed by Sanofi S.A. and may hold shares and/or stock options in the company. The remaining Topic Editors declare no commercial or financial relationships that could be construed as a potential conflict of interest. Topic editors: Mitsunori Nomura, Nagakannan Pandian, Matija Zelic Source: https://www.frontiersin.org/research-topics/81550/beyond-apoptosis-molecular-mechanisms-of-regulated-cell-death-in-the-nervous-system