TABLE 1.

Necroptosis in acute neurodegenerative diseases.

Disease	Regulatory factors	Synthetic inhibitors	Comment	Reference
Traumatic brain injury	RIPK1	Nec-1	Hypothermia inhibited necroptosis pathway though down-regulation of RIPK1, in moderate TBI models of rats.	The, (2018)
			Necrostatin-1 inhibited apoptosis and autophagy simultaneously.	Wang et al. (2012)
	RIPK3		Oxidative stress, inflammation and apoptosis in astrocytes, which dependent on AMPKa activation, were attenuated by RIPK3-ablation.	Lakhan et al. (2009)
			RIPK3-knockout (KO) attenuated cognitive dysfunction and activation of glia cells in TBI injuryed mice	Lakhan et al. (2009)
	MLKL		RIPK1, MLKL and pro-inflammation cytokines increased in rat FPI models.	Zhang et al. (2017b)
Stroke	NLRP3		NLRP3 inflammasome was found in both immune cells and necroptotic neuron when caspase is inhibited by Q-VD-OPH	Bai et al. (2019)
	RIPK1	Nec-1	Pretreatment with Necrostatin-1 ameliorated cell death by reducing the interact of increased RIPK3 with RIPK1.	Teng et al. (2018)
	RIPK3		Expression level of RIPK3 was increased after ICH.	Teng et al. (2018)
Encephalitis	MLKL		In mice model, the expression of MLKL in neurons was upregulated when JEV infected, while deletion of MLKL mitigated the progression of JE and down-regulated the level of inflammatory factors.	Bian et al. (2017)
	RIPK3		RIPK3 restricts WNV pathogenesis by inhibiting necroptosis in a mouse WNV encephalitis.	Barnett, (2019)
			RIPK3-/- mice was more likely to survive compared to wild-type controls, while lacking the necroptotic effectors (such as MLKL, or both MLKL and caspase-8)	Barnett, (2019)

FBI, Fluid precussion injury; ICH, Intracerebral hemorrhage; JEV, Japanese encephalitis virus; MLKL, Mixed lineage kinase domain-like protein; Nec-1, Necrostatin-1; NLRP3, NLR Family Pyrin Domain Containing 3; RIPK1, Receptor-interacting protein kinase 1; RIPK3, Receptor-interacting protein kinase 3; TBI, Traumatic brain injury; WNV, West Nile Virus.