Necroptosis in ALS: a hot topic in-progress

摘要

Necroptosis is triggered by inflammatory mediators, including TNF-α and FasL. Upon the recruitment of adapter proteins, the phosphorylation of RIPK1 is induced. The necrosome is composed of interaction and activation (i.e. phosphorylation) of RIPK1, RIPK3, and MLKL. Necroptosis of the cell is induced by mitochondrial fission through interaction of MLKL with mitochondrial phosphatase PGAM5 and Drp1 recruitment. Phosphorylated MLKL also triggers cell death through the disruption of the plasma membrane integrity1,2. Other mechanisms by which MLKL induces cell death remains to be elucidated. Pharmacological or genetic modulations (⊥) of necroptosis signaling can target RIPK1, RIPK3, MLKL, as well as their phosphorylated forms12–14. Drp1 dynamin-related protein 1, FADD Fas-associated protein with Death Domain, Fas-L Fas-ligand, MLKL mixed lineage kinases domain-like, p phosphorylated, PGAM5 phosphoglycerate mutase family member 5, RIPK receptor-interacting protein kinases, TNFα tumor necrosis factor α, TNFR1 tumor necrosis factor receptor 1, TRADD tumor necrosis factor receptor type 1-associated death.