Necroptosis

Necroptosis is a form of programmed necrotic cell death that proceeds through a defined molecular pathway involving receptor-interacting protein kinases RIPK1 and RIPK3 and the pseudokinase MLKL; when apoptosis is blocked or overwhelmed, RIPK3-mediated phosphorylation of MLKL drives its oligomerisation and plasma-membrane translocation, causing lytic membrane disruption and the release of damage-associated molecular patterns (DAMPs). Unlike apoptosis, necroptosis is inherently inflammatory due to this DAMP release, and it can be triggered by death-receptor ligands, viral sensors and toll-like receptors. Emerging evidence links necroptosis to age-related pathologies including neurodegeneration, ischaemic injury and inflammatory bowel disease, though its specific contribution to physiological ageing versus acute disease remains under investigation.