Targeting necroptosis: a promising avenue for respiratory disease treatment

Respiratory diseases are a growing concern in public health because of their potential to endanger the global community. Cell death contributes critically to the pathophysiology of respiratory diseases. Recent evidence indicates that necroptosis, a unique form of programmed cell death (PCD), plays a vital role in the molecular mechanisms underlying respiratory diseases, distinguishing it from apoptosis and conventional necrosis. Necroptosis is a type of inflammatory cell death governed by receptor-interacting serine/threonine protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like protein (MLKL), resulting in the release of intracellular contents and inflammatory factors capable of initiating an inflammatory response in adjacent tissues. These necroinflammatory conditions can result in significant organ dysfunction and long-lasting tissue damage within the lungs. Despite evidence linking necroptosis to various respiratory diseases, there are currently no specific alternative treatments that target this mechanism. This review provides a comprehensive overview of the most recent advancements in understanding the significance and mechanisms of necroptosis. Specifically, this review emphasizes the intricate association between necroptosis and respiratory diseases, highlighting the potential use of necroptosis as an innovative therapeutic approach for treating these conditions.