Mixed lineage kinase domain-like protein (MLKL) mRNA (MLKL mRNA)

Mixed lineage kinase domain-like protein (MLKL) mRNA encodes the terminal effector protein of the necroptosis pathway, a form of programmed necrotic cell death (PMID: 24316671). In response to pro-inflammatory stimuli and the activation of RIPK1 and RIPK3 kinases, the MLKL protein is phosphorylated, leading to its oligomerization and translocation to the plasma membrane where it causes rupture (UniProt Q8NB16). Targeting the MLKL mRNA using antisense oligonucleotides (ASOs) or siRNA allows for the depletion of the MLKL protein pool, effectively blocking necroptosis regardless of the upstream stimulus (PMID: 28842598). This approach is being explored for the treatment of various inflammatory and ischemic diseases where excessive necroptosis contributes to tissue damage, such as kidney injury and inflammatory bowel disease (PMID: 30104312). By preventing the synthesis of MLKL, these therapies aim to mitigate the inflammatory response and cellular loss associated with chronic inflammation and acute injury.

Other names

Mixed lineage kinase domain-like transcriptMLKL messenger RNAMLKL mRNA

Reduction of MLKL protein expression via RNase H-mediated degradation of mRNA or RNA interference, preventing the formation of the necrosome-induced membrane pore.