Regulated cell death in thyroid follicular cells: Molecular insights into pyroptosis, apoptosis, and necrosis

Abstract

Programmed cell death (PCD) pathways are crucial for eliminating functionally redundant, infected, or potentially tumorigenic cells. They play significant roles in maintaining homeostasis, defending against pathogens, preventing cancer, and addressing various other pathologies. Multiple PCD pathways, including apoptosis, necroptosis, and pyroptosis, have been well-characterized. Different molecular and cellular functions are included in these pathways, and each of these processes results in different cellular outcomes, including the activation of inflammatory responses. This review aims to investigate the molecular components that regulate apoptosis, pyroptosis, and necroptosis, with a particular emphasis on the interaction pathways between these processes in the context of thyroid follicular cell death. It aims to examine the implications of these pathways for thyroid health and disease, as well as providing an in-depth understanding of the flexible and coordinated nature of PCD pathways in thyroid cells, emphasizing their interconnectedness and the plasticity of their molecular regulation. It underscores the potential of using this flexibility in therapeutic strategies for thyroid-related disorders. Significant plasticity has been observed in the regulation of PCD pathways in recent genetic and biochemical investigations. Apoptosis can be induced by inflammatory caspases, for example, that usually cause pyroptosis, and the stimulus of apoptosis can induce pyroptosis. This flexibility is particularly evident in the cellular response to infections. Understanding the coordinated regulation of different PCD pathways could open new avenues for targeted therapeutic interventions in thyroid diseases, potentially improving treatment outcomes for thyroid-related disorders.