Sterile Neuroinflammation and Strategies for Therapeutic Intervention

Table 2

A list of drugs that ameliorate DAMPs-induced neuroinflammation.

Mode	Drug	Remarks	References
Inhibition of DAMPs release	VIP, urocortin, PACAP, acetyl choline	Endogenous, inhibiting nucleus-to-cytoplasm transport of HMGB1	[160–162]
	EP	Inhibiting nucleus-to-cytoplasm transport of HMGB1	[173, 174]
	MK-801	Blocking glutamate/NMDA receptor, reducing HMGB1 release	[163]
	EPA	PPARγ agonist, attenuating HMGB1 release	[164]
	GL	Constituting licorice root, inhibiting HMGB1 release	[161, 165, 166]
	CBX	Synthetic GL, reducing HMGB1 secretion	[167]
	Tanshinones	Constituting herb “Danshen”, inhibiting HMGB1 release	[168]
	Atorvastatin, simvastatin	Attenuating the extracellular release of HMGB1	[169]
	NM, GM, sivelestat	Synthetic, inhibiting HMGB1 secretion	[170–172]
Neutralization of DAMPs	HMGB1 A box	HMGB1 lacking proinflammatory activity, competitively inhibits HMGB1	[161, 175–177]
	Anti-HMGB1 antibody	Reduction in proinflammatory role	[179]
	Aβ vaccine	Generation of anti-Aβ antibodies	[180]
Blockade of DAMPs-specific receptors	VIPER	Peptide, blocking TLR4	[204]
	Anti-TLR2 antibody	Reduction in proinflammatory role	[182]
	Anti-TLR4 antibody	Reduction in proinflammatory role	[182]
	RAGE vaccine	RAGE/Aβ complex has greater immunogenic response than RAGE or Aβ alone	[180]
	S100P-derived peptide	Competitive inhibitor of RAGE	[161, 183]
	FPS-ZM1	RAGE specific antagonist	[184]
	MCC950	Potent, selective inhibitor of NLRP3	[186]
	IL-1RA	Blocking IL-1R	[187]
Inhibition of signaling pathways downstream of receptors	Resveratrol	Natural polyphenol	[189]
	Exogenous PACAP	Inhibiting the upregulation of TLR4, MyD88, P-IκB, and NF-κB	[190]
	MTX	HMGB1 binding property, reducing HMGB1/RAGE interaction	[191]
	Simvastatin	Attenuating TLR4 and NF-κB expression	[192]
	Luteolin	Fruit and vegetable constituent, downregulating TLR4 and NF-κB	[194]
	Tan IIA	Reducing the expression of HMGB1, TLR4, RAGE, and NF-κB	[193]
	MLN519	Protease inhibitor, modulating NF-κB activity	[195]
Activation of DAMPs clearance	MTC	Inhibiting tau aggregation	[202]

VIP, vasoactive intestinal peptide; PACAP, pituitary adenylate cyclase-activating polypeptide; EP, ethyl pyruvate; EPA, eicosapentaenoic acid; PPARγ, peroxisome proliferator-activated receptor gamma; GL, glycyrrhizin; CBX, carbenoxolone; NM, nafamostat mesilate; GM, gabexate mesilate; VIPER, viral inhibitory peptide; FPS-ZM1, n-benzyl-4-chloro-N-cyclohexylbenzamide; IL-1RA, IL-1 receptor antagonist; MTX, methotrexate; Tan IIA, tanshinone II A; MTC, methylthioninium chloride.