2.1 Necroptosis signal pathway
Cellula demise is a key factor in keeping homeostasis in organisms, and it is also a way to remove impaired, infected or degraded cells (Vaux and Korsmeyer 1999). In an adult, approximately ten to one hundred billion cells die per day and are substituted by new healthy cells to keep the homeostasis of the entire body (Glucksmann 1951). Therefore, it is obvious that when the balance between cell death and cell proliferation is disrupted, various abnormal reactions and diseases of the body will be caused (Renehan, Booth and Potten 2001). In the past, apoptosis has always been regarded as the only form of RCD, until the first genetic determinant of death receptor-induced necroptosis, receptor-interacting serine/threonine-protein kinase 1 (RIPK1), was found (Holler et al. 2000). Whereas the term of necroptosis used to express this nonapoptotic RCD form was created until 2005 (Degterev et al. 2005). Apoptosis is a caspase-dependent RCD which characterized by cell membrane blistering, cell contraction, nuclear fracturing, chromosome concentration and chromosomal DNA fragmentation(Kerr, Wyllie and Currie 1972). Different from apoptosis, necroptosis is a type caspase-independent RCD form which characterized by increased cell membrane permeability, plasmalemma ruptures, general swelling of cytoplasm and organelles, and overflow of cell components into the microenvironment (Galluzzi et al. 2017) (show in Fig 2). Present Studies have shown that necroptosis is mainly mediated by RIPK1, RIPK3, and mixed lineage kinase-like protein (MLKL) (Frank and Vince 2019).