Regulated Cell Death in Health and Disease: Emerging Mechanisms and Clinical Implications

Abstract

Programmed cell death (PCD) is a tightly regulated biological process indispensable for preserving cellular homeostasis and directing tissue development. Perturbations in PCD pathways—including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy—have come to be increasingly linked with the initiation and promotion of various human diseases, including cancer, cardiovascular disease, neurodegenerative disorders, and diabetes. The review critically reviews the mechanisms that control these pathways of cell death as well as their pathobiological significance across disease models. Specific focus is put on ferroptosis and PAN optosis as novel targets for therapy, with potential for breaking through cancer drug resistance as well as for maintaining cardiomyocyte viability during ischemic heart disease. Roles of necroptosis and pyroptosis in facilitating neuroinflammation and tissue damage are further discussed in the context of Alzheimer's and Parkinson's disease as well as in diabetic complications. The latest reports on ubiquitination and cross-talk among pathways shed light on a highly complex, interdependent world of cell death regulation, paving the way for multi-target therapeutics. By converging molecular knowledge with disease-specific translation, this review identifies emerging paths for the construction of precision drugs to modulate cell death in the clinic.