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.