Regulated cell death in COPD: Modulators, crosstalk mechanisms, and therapeutic opportunities

Chronic obstructive pulmonary disease (COPD) involves multiple forms of regulated cell death (RCD) that may impact disease progression.

• Regulated cell death pathways, including apoptosis, necroptosis, ferroptosis, pyroptosis, NETosis, and PANoptosis, are implicated in the pathogenesis of COPD.
• Common regulatory factors across RCD types include membrane receptors, epigenetic modifications, and post-translational processes.
• Excessive endoplasmic reticulum stress can trigger apoptosis, while impaired autophagy may lead to oxidative stress and inflammation.
• Crosstalk between RCD pathways suggests that macrophage inflammation can exacerbate epithelial cell death and inflammatory responses.
• Ferroptosis in airway epithelial cells may worsen pyroptosis, indicating a complex interplay between different cell death mechanisms.
• Current therapeutic strategies explore targeting these regulated cell death pathways using various agents, including pharmaceuticals and regenerative therapies.

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