Regulated cell death in the nervous system: a framework for execution diversity and spatially restricted degeneration

Abstract

Regulated cell death (RCD) encompasses genetically encoded and pharmacologically modifiable pathways that govern cellular demise. In the nervous system, RCD assumes unique biological and clinical relevance due to neurons’ post-mitotic status, the functional integration of neural circuits, and the central role of glial cells in homeostasis and inflammation. This review synthesizes current knowledge on apoptotic and non-apoptotic RCD modalities in neurons and glia, integrates molecular mechanisms with ultrastructural hallmarks, and discusses specific patterns of pathway engagement. We emphasize compartmentalized death, pathway crosstalk, and cell-type specificity.