Apoptotic and necroptotic signaling pathways (PCD pathways)

Apoptotic and necroptotic signaling pathways are the primary mechanisms of regulated cell death (RCD) essential for development and tissue homeostasis (Galluzzi et al., 2018). Apoptosis is a non-inflammatory process characterized by caspase activation and mitochondrial outer membrane permeabilization (MOMP), often evaded by cancer cells to ensure survival (Fuchs & Steller, 2011). Necroptosis is a regulated form of necrosis mediated by the RIPK1-RIPK3-MLKL axis, which triggers plasma membrane rupture and the release of pro-inflammatory damage-associated molecular patterns (DAMPs) (Pasparakis & Vandenabeele, 2015). These pathways are critical therapeutic targets; for example, BCL-2 inhibitors like venetoclax restore apoptosis in hematologic malignancies, while RIPK1 inhibitors are being investigated to treat inflammatory and neurodegenerative diseases (Dhuriya & Sharma, 2018). However, targeting these pathways requires precision to avoid systemic toxicity or unintended inflammatory responses (Yuan et al., 2019). The interplay between these pathways highlights the complexity of targeting cell death in clinical settings (Malireddi et al., 2019).

Other names

Programmed cell deathRegulated cell deathApoptosis and necroptosis signalingRCD pathways

Modulation of programmed cell death through the inhibition of anti-apoptotic proteins (e.g., BCL-2), inhibition of necroptotic kinases (e.g., RIPK1, RIPK3), or activation of pro-apoptotic signaling cascades.