Insight into Crosstalk between Ferroptosis and Necroptosis: Novel Therapeutics in Ischemic Stroke

Table 1

Schematic overview of ferroptosis and necroptosis in ischemic stroke. JAK: Janus kinase; STEAP3: six-transmembrane epithelial antigen of prostate 3; ACSL4: acyl-CoA synthetase long-chain family member 4; FPN: ferroportin; TFR1: transferrin receptor 1; PHKG2: phosphorylase kinase G2; NADPH: nicotinamide adenine dinucleotide phosphate; TNFR: tumor necrosis factor receptor; DFO: deferoxamine; Nec-1: necrostatin-1.

	Ferroptosis	Necroptosis
Morphological characteristics	Shrunken mitochondria, fragmented mitochondria, enlarged cristae, dense membrane, lipid radicals	Necrosomes, ion-selective channels formed by MLKL, round and swollen cells, broken plasma membrane
Developmental steps	Iron overload, GSH depletion, GPX4 inactivation, lipid peroxidation, system xc^- impairment	RIP1 activation, RIP3 and MLKL phosphorylation
Key regulators	GPX4, JAK, STEAP3, TFR1, ACSL4, FPN, PHKG2, p53, NADPH oxidase	RIP1, RIP3, MLKL, Fas/TNFR, p53
Inducers and inhibitors	Inducers: erastin [22], sorafenib [23], acrolein [22]; Inhibitors: DFO [24], vitamin B12 [25], carvacrol [26], Chinese herbal medicines including naotaifang [27]	Inducers: alkylating agents [28], X-rays [29]; Inhibitors: Nec-1 [30], infliximab [7], dabrafenib [31], Chinese herbal medicines including curcumin [32]