Table Info

Table 1.

The underlying mechanism of several NLRP3 inflammasome inhibitors

Sr no.	NLRP3 inflammasome inhibitor	Models	Molecular mechanisms of NLRP3 activation	References
1	JC-124	TgCRND8 mice	Inhibited activation of NLRP3 inflammasome and reduced Aβ sedimentation and soluble and insoluble Aβ1–42 level	[96]
2	NSAIDs	3×TgAD transgenic mice	Inhibited the release of IL-1β, inhibited cognitive impairment	[51]
3	MCC950	APP/PS1 mice	Inhibited the activation of NLRP3 inflammasome and microglia, inhibited CASP1 activation and IL-1β release, reduced the accumulation of Aβ	[97]
4	Dl-NBP	APP/PS1 mice	Inhibited the expression of Nrf2, and the activation of NLRP3 inflammasome	[98]
5	Artemisinin	APPswe/PS-1dE9 transgenic mice	Reduced the activation of NF-κB and NLRP3 inflammatory corpuscles, and the Aβ deposition	[99]
6	DHM	APP/PS1 mice	Down-regulated the expression of NLRP3 inflammasome components NLRP3, ASC and CASP1 and reduced the release of IL-1β	[81]
7	EVOO	TgSwDI mice	Inhibited NACHT, LRR and PYD NLRP3 inflammasome	[100]
8	CS	APP/PS1 mice	Reduced Aβ deposition and microglia, inhibited NLRP3 inflammasome activation and restored synaptic membrane formation, and improved cognitive deficits	[101]
9	Edaravone	Aβ₁₋₄₂ activated BV-2 microglia	Attenuated the depolarization of Δψm, reduced the production of ROS, and increased the activity of SOD-2, inhibited IL-1β secretion	[102]
10	BITC	LPS-induced BV2 microglia	Inhibited the activation of NLRP3 inflammasomes, and reduced pro-inflammatory mediator levels, including mtROS and ATP secretion	[103]
11	Pterostilbene	Aβ_1–42-induced BV-2 cells	Reduced the expression and secretion levels of IL-6, IL-1β and TNF-α	[104]
12	Stavudine	THP-1-derived macrophages were stimulated with Aβ42 or with Aβ42 after LPS-priming	Reduced the assembly of NLRP3 and the production of IL-18 and CASP1	[105]
13	VX-765	J20 mice	Prevented progressive Aβ peptide deposition, reversed brain inflammation, and normalized hippocampal synaptophysin levels	[106]
14	GRg3	Intracerebral LPS injection in SD rats	Reduced LPS-induced cognitive impairment by inhibiting the expression of proinflammatory mediators in the hippocampus	[107]

NSAIDs: non-steroidal anti-inflammatory drugs; Dl-NBP: Dl-3-n-butylphthalide; DHM: dihydromyricetin; EVOO: extra virgin olive oil; CS: choline supplementation; BITC: benzyl isothiocyanate; GRg3: Ginsenoside Rg3; SOD-2: superoxide dismutase-2; TNF-α: tumour necrosis factor alpha

Declarations

Author contributions

XG wrote the original draft of the manuscript; XZ, YS and XD wrote the review; XZ edited the review; XG, YS and XD revised the manuscript; XD conceptualized the manuscript and made the funding acquisition. All authors contributed to manuscript revision, read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This research was supported by grants from the Beijing Natural Science Foundation (6164030), 2019 Basic Research Projects of Beijing Union University, Beijing Key Laboratory of Bioactive Substances and Functional Foods Research Project, the Academic Research Projects of Beijing Union University (No. ZK80202102, XP202007), and Graduate Funding Project in Beijing Union University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Long JM, Holtzman DM. Alzheimer disease: an update on pathobiology and treatment strategies. Cell. 2019;179:312–39. [DOI] [PubMed] [PMC]

Tiwari S, Atluri V, Kaushik A, Yndart A, Nair M. Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics. Int J Nanomedicine. 2019;14:5541–54. [DOI] [PubMed] [PMC]

Saresella M, La Rosa F, Piancone F, Zoppis M, Marventano I, Calabrese E, et al. The NLRP3 and NLRP1 inflammasomes are activated in Alzheimer’s disease. Mol Neurodegener. 2016;11:23. [DOI] [PubMed] [PMC]

Hansen DV, Hanson JE, Sheng M. Microglia in Alzheimer’s disease. J Cell Biol. 2018;217:459–72. [DOI] [PubMed] [PMC]

Gold M, El Khoury J. β-amyloid, microglia, and the inflammasome in Alzheimer’s disease. Semin Immunopathol. 2015;37:607–11. [DOI] [PubMed] [PMC]

Prinz M, Jung S, Priller J. Microglia biology: one century of evolving concepts. Cell. 2019;179:292–311. [DOI] [PubMed]

Breitner JC, Baker LD, Montine TJ, Meinert CL, Lyketsos CG, Ashe KH, et al. Extended results of the Alzheimer’s disease anti-inflammatory prevention trial. Alzheimers Dement. 2011;7:402–11. [DOI] [PubMed] [PMC]

Freeman L, Guo H, David CN, Brickey WJ, Jha S, Ting JP. NLR members NLRC4 and NLRP3 mediate sterile inflammasome activation in microglia and astrocytes. J Exp Med. 2017;214:1351–70. [DOI] [PubMed] [PMC]

Zhang P, Cao L, Zhou R, Yang X, Wu M. The lncRNA Neat1 promotes activation of inflammasomes in macrophages. Nat Commun. 2019;10:1495. [DOI] [PubMed] [PMC]

10.

Ismael S, Zhao L, Nasoohi S, Ishrat T. Inhibition of the NLRP3-inflammasome as a potential approach for neuroprotection after stroke. Sci Rep. 2018;8:5971. [DOI] [PubMed] [PMC]

11.

Ferreira NS, Bruder-Nascimento T, Pereira CA, Zanotto CZ, Prado DS, Silva JF, et al. NLRP3 inflammasome and mineralocorticoid receptors are associated with vascular dysfunction in type 2 diabetes mellitus. Cells. 2019;8:1595. [DOI] [PubMed] [PMC]

12.

Guo C, Fu R, Wang S, Huang Y, Li X, Zhou M, et al. NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid arthritis. Clin Exp Immunol. 2018;194:231–43. [DOI] [PubMed] [PMC]

13.

Han X, Sun S, Sun Y, Song Q, Zhu J, Song N, et al. Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: implications for Parkinson disease. Autophagy. 2019;15:1860–81. [DOI] [PubMed] [PMC]

14.

Fusco R, Siracusa R, Genovese T, Cuzzocrea S, Di Paola R. Focus on the role of NLRP3 inflammasome in diseases. Int J Mol Sci. 2020;21:4223. [DOI] [PubMed] [PMC]

15.

Codolo G, Plotegher N, Pozzobon T, Brucale M, Tessari I, Bubacco L, et al. Triggering of inflammasome by aggregated alpha-synuclein, an inflammatory response in synucleinopathies. PLoS One. 2013;8:e55375. [DOI] [PubMed] [PMC]

16.

Brubaker SW, Bonham KS, Zanoni I, Kagan JC. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015;33:257–90. [DOI] [PubMed] [PMC]

17.

Howrylak JA, Nakahira K. Inflammasomes: key mediators of lung immunity. Annu Rev Physiol. 2017;79:471–94. [DOI] [PubMed]

18.

Ozaki E, Campbell M, Doyle SL. Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives. J Inflamm Res. 2015;8:15–27. [DOI] [PubMed] [PMC]

19.

Wang S, Yuan YH, Chen NH, Wang HB. The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in Parkinson’s disease. Int Immunopharmacol. 2019;67:458–64. [DOI] [PubMed]

20.

Li Y, Fu TM, Lu A, Witt K, Ruan J, Shen C, et al. Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1. Proc Natl Acad Sci U S A. 2018;115:10845–52. [DOI] [PubMed] [PMC]

21.

Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140:821–32. [DOI] [PubMed]

22.

Song L, Pei L, Yao S, Wu Y, Shang Y. NLRP3 inflammasome in neurological diseases, from functions to therapies. Front Cell Neurosci. 2017;11:63. [DOI] [PubMed] [PMC]

23.

Hoss F, Rodriguez-Alcazar JF, Latz E. Assembly and regulation of ASC specks. Cell Mol Life Sci. 2017;74:1211–29. [DOI] [PubMed]

24.

Mambwe B, Neo K, Javanmard Khameneh H, Leong KWK, Colantuoni M, Vacca M, et al. Tyrosine dephosphorylation of ASC modulates the activation of the NLRP3 and AIM2 inflammasomes. Front Immunol. 2019;10:1556. [DOI] [PubMed] [PMC]

25.

Py BF, Kim MS, Vakifahmetoglu-Norberg H, Yuan J. Deubiquitination of NLRP3 by BRCC3 critically regulates inflammasome activity. Mol Cell. 2013;49:331–8. [DOI] [PubMed]

26.

Shao BZ, Xu ZQ, Han BZ, Su DF, Liu C. NLRP3 inflammasome and its inhibitors: a review. Front Pharmacol. 2015;6:262. [DOI] [PubMed] [PMC]

27.

Muñoz-Planillo R, Kuffa P, Martínez-Colón G, Smith BL, Rajendiran TM, Núñez G. K⁺ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity. 2013;38:1142–53. [DOI] [PubMed] [PMC]

28.

Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011;469:221–5. [DOI] [PubMed]

29.

Heid ME, Keyel PA, Kamga C, Shiva S, Watkins SC, Salter RD. Mitochondrial reactive oxygen species induces NLRP3-dependent lysosomal damage and inflammasome activation. J Immunol. 2013;191:5230–8. [DOI] [PubMed] [PMC]

30.

Liu Q, Zhang D, Hu D, Zhou X, Zhou Y. The role of mitochondria in NLRP3 inflammasome activation. Mol Immunol. 2018;103:115–24. [DOI] [PubMed]

31.

Minutoli L, Puzzolo D, Rinaldi M, Irrera N, Marini H, Arcoraci V, et al. ROS-mediated NLRP3 inflammasome activation in brain, heart, kidney, and testis ischemia/reperfusion injury. Oxid Med Cell Longev. 2016;2016:2183026. [DOI] [PubMed] [PMC]

32.

Li L, Ismael S, Nasoohi S, Sakata K, Liao FF, McDonald MP, et al. Thioredoxin-interacting protein (TXNIP) associated NLRP3 inflammasome activation in human Alzheimer’s disease brain. J Alzheimers Dis. 2019;68:255–65. [DOI] [PubMed]

33.

Muri J, Thut H, Feng Q, Kopf M. Thioredoxin-1 distinctly promotes NF-kappaB target DNA binding and NLRP3 inflammasome activation independently of Txnip. Elife. 2020;9:e53627. [DOI] [PubMed] [PMC]

34.

Sun X, Jiao X, Ma Y, Liu Y, Zhang L, He Y, et al. Trimethylamine N-oxide induces inflammation and endothelial dysfunction in human umbilical vein endothelial cells via activating ROS-TXNIP-NLRP3 inflammasome. Biochem Biophys Res Commun. 2016;481:63–70. [DOI] [PubMed]

35.

He X, Ma Q. Redox regulation by nuclear factor erythroid 2-related factor 2: gatekeeping for the basal and diabetes-induced expression of thioredoxin-interacting protein. Mol pharmacol. 2012;82:887–97. [DOI] [PubMed] [PMC]

36.

Hou Y, Wang Y, He Q, Li L, Xie H, Zhao Y, et al. Nrf2 inhibits NLRP3 inflammasome activation through regulating Trx1/TXNIP complex in cerebral ischemia reperfusion injury. Behav Brain Res. 2018;336:32–9. [DOI] [PubMed]

37.

Jiao P, Li W, Shen L, Li Y, Yu L, Liu Z. The protective effect of doxofylline against lipopolysaccharides (LPS)-induced activation of NLRP3 inflammasome is mediated by SIRT1 in human pulmonary bronchial epithelial cells. Artif Cells Nanomed Biotechnol. 2020;48:687–94. [DOI] [PubMed]

38.

Kim SM, Ha JS, Han AR, Cho SW, Yang SJ. Effects of α-lipoic acid on LPS-induced neuroinflammation and NLRP3 inflammasome activation through the regulation of BV-2 microglial cells activation. BMB Rep. 2019;52:613–8. [DOI] [PubMed] [PMC]

39.

Han X, Wu YC, Meng M, Sun QS, Gao SM, Sun H. Linarin prevents LPS-induced acute lung injury by suppressing oxidative stress and inflammation via inhibition of TXNIP/NLRP3 and NF-κB pathways. Int J Mol Med. 2018;42:1460–72. [DOI] [PubMed] [PMC]

40.

Liu H, You L, Wu J, Zhao M, Guo R, Zhang H, et al. Berberine suppresses influenza virus-triggered NLRP3 inflammasome activation in macrophages by inducing mitophagy and decreasing mitochondrial ROS. J Leukoc Biol. 2020;108:253–66. [DOI] [PubMed]

41.

Gong T, Yang Y, Jin T, Jiang W, Zhou R. Orchestration of NLRP3 inflammasome activation by ion fluxes. Trends Immunol. 2018;39:393–406. [DOI] [PubMed]

42.

Pétrilli V, Papin S, Dostert C, Mayor A, Martinon F, Tschopp J. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 2007;14:1583–9. [DOI] [PubMed]

43.

He Y, Zeng MY, Yang D, Motro B, Núñez G. NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature. 2016;530:354–7. [DOI] [PubMed] [PMC]

44.

Green JP, Yu S, Martin-Sánchez F, Pelegrin P, Lopez-Castejon G, Lawrence CB, et al. Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming. Proc Natl Acad Sci U S A. 2018;115:E9371–80. [DOI] [PubMed] [PMC]

45.

Chen Y, Meng J, Bi F, Li H, Chang C, Ji C, et al. EK7 regulates NLRP3 inflammasome activation and neuroinflammation post-traumatic brain injury. Front Mol Neurosci. 2019;12:202. [DOI] [PubMed] [PMC]

46.

Wang D, Wang H, Gao H, Zhang H, Zhang H, Wang Q, et al. P2X7 receptor mediates NLRP3 inflammasome activation in depression and diabetes. Cell Biosci. 2020;10:28. [DOI] [PubMed] [PMC]

47.

Karmakar M, Katsnelson MA, Dubyak GR, Pearlman E. Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1beta secretion in response to ATP. Nat Commun. 2016;7:10555. [DOI] [PubMed] [PMC]

48.

Di A, Xiong S, Ye Z, Malireddi RKS, Kometani S, Zhong M, et al. The TWIK2 potassium efflux channel in macrophages mediates NLRP3 inflammasome-induced inflammation. Immunity. 2018;49:56–65.e4. [DOI] [PubMed] [PMC]

49.

Groß CJ, Mishra R, Schneider KS, Médard G, Wettmarshausen J, Dittlein DC, et al. K⁺ efflux-independent NLRP3 inflammasome activation by small molecules targeting mitochondria. Immunity. 2016;45:761–73. [DOI] [PubMed]

50.

Compan V, Baroja-Mazo A, López-Castejón G, Gomez AI, Martínez CM, Angosto D, et al. Cell volume regulation modulates NLRP3 inflammasome activation. Immunity. 2012;37:487–500. [DOI] [PubMed]

51.

Daniels MJ, Rivers-Auty J, Schilling T, Spencer NG, Watremez W, Fasolino V, et al. Fenamate NSAIDs inhibit the NLRP3 inflammasome and protect against Alzheimer’s disease in rodent models. Nat Commun. 2016;7:12504. [DOI] [PubMed] [PMC]

52.

Tang T, Lang X, Xu C, Wang X, Gong T, Yang Y, et al. CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation. Nat Commun. 2017;8:202. [DOI] [PubMed] [PMC]

53.

Murakami T, Ockinger J, Yu J, Byles V, McColl A, Hofer AM, et al. Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proc Natl Acad Sci U S A. 2012;109:11282–7. [DOI] [PubMed] [PMC]

54.

Katsnelson MA, Lozada-Soto KM, Russo HM, Miller BA, Dubyak GR. NLRP3 inflammasome signaling is activated by low-level lysosome disruption but inhibited by extensive lysosome disruption: roles for K⁺ efflux and Ca²⁺ influx. Am J Physiol Cell Physiol. 2016;311:C83–100. [DOI] [PubMed] [PMC]

55.

Lee GS, Subramanian N, Kim AI, Aksentijevich I, Goldbach-Mansky R, Sacks DB, et al. The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca²⁺ and cAMP. Nature. 2012;492:123–7. [DOI] [PubMed] [PMC]

56.

Xu M, Jiang Z, Wang C, Li N, Bo L, Zha Y, et al. Acetate attenuates inflammasome activation through GPR43-mediated Ca²⁺-dependent NLRP3 ubiquitination. Exp Mol Med. 2019;51:1–13. [DOI] [PubMed] [PMC]

57.

Tseng HH, Vong CT, Kwan YW, Lee SM, Hoi MP. TRPM2 regulates TXNIP-mediated NLRP3 inflammasome activation via interaction with p47 phox under high glucose in human monocytic cells. Sci Rep. 2016;6:35016. [DOI] [PubMed] [PMC]

58.

Wu X, Ren G, Zhou R, Ge J, Chen FH. The role of Ca²⁺ in acid-sensing ion channel 1a-mediated chondrocyte pyroptosis in rat adjuvant arthritis. Lab Invest. 2019;99:499–513. [DOI] [PubMed]

59.

Zhong Z, Liang S, Sanchez-Lopez E, He F, Shalapour S, Lin XJ, et al. New mitochondrial DNA synthesis enables NLRP3 inflammasome activation. Nature. 2018;560:198–203. [DOI] [PubMed] [PMC]

60.

Yang Y, Wang H, Kouadir M, Song H, Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis. 2019;10:128. [DOI] [PubMed] [PMC]

61.

Lupfer CR, Rodriguez A, Kanneganti TD. Inflammasome activation by nucleic acids and nucleosomes in sterile inflammation... or is it sterile? FEBS J. 2017;284:2363–74. [DOI] [PubMed] [PMC]

62.

Pereira CA, Carlos D, Ferreira NS, Silva JF, Zanotto CZ, Zamboni DS, et al. Mitochondrial DNA promotes NLRP3 inflammasome activation and contributes to endothelial dysfunction and inflammation in type 1 diabetes. Front Physiol. 2020;10:1557. [DOI] [PubMed] [PMC]

63.

Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC, et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol. 2011;12:222–30. [DOI] [PubMed] [PMC]

64.

Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N, Chen S, et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 2012;36:401–14. [DOI] [PubMed] [PMC]

65.

Coll RC, Holley CL, Schroder K. Mitochondrial DNA synthesis fuels NLRP3 activation. Cell Res. 2018;28:1046–7. [DOI] [PubMed] [PMC]

66.

Hornung V, Latz E. Critical functions of priming and lysosomal damage for NLRP3 activation. Eur J Immunol. 2010;40:620–3. [DOI] [PubMed] [PMC]

67.

Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008;9:847–56. [DOI] [PubMed] [PMC]

68.

Chen N, Ou Z, Zhang W, Zhu X, Li P, Gong J. Cathepsin B regulates non-canonical NLRP3 inflammasome pathway by modulating activation of caspase-11 in Kupffer cells. Cell Prolif. 2018;51:e12487. [DOI] [PubMed] [PMC]

69.

Chevriaux A, Pilot T, Derangère V, Simonin H, Martine P, Chalmin F, et al. Cathepsin B is required for NLRP3 inflammasome activation in macrophages, through NLRP3 interaction. Front Cell Dev Biol. 2020;8:167. [DOI] [PubMed] [PMC]

70.

Bai H, Yang B, Yu W, Xiao Y, Yu D, Zhang Q. Cathepsin B links oxidative stress to the activation of NLRP3 inflammasome. Exp Cell Res. 2018;362:180–7. [DOI] [PubMed]

71.

Wang D, Zhang J, Jiang W, Cao Z, Zhao F, Cai T, et al. The role of NLRP3-CASP1 in inflammasome-mediated neuroinflammation and autophagy dysfunction in manganese-induced, hippocampal-dependent impairment of learning and memory ability. Autophagy. 2017;13:914–27. [DOI] [PubMed] [PMC]

72.

Gouras GK, Olsson TT, Hansson O. β-amyloid peptides and amyloid plaques in Alzheimer’s disease. Neurotherapeutics. 2015;12:3–11. [DOI] [PubMed] [PMC]

73.

Yang J, Wise L, Fukuchi KI. TLR4 cross-talk with NLRP3 inflammasome and complement signaling pathways in Alzheimer’s disease. Front Immunol 2020;11:724. [DOI] [PubMed] [PMC]

74.

Kim N, Do J, Ju IG, Jeon SH, Lee JK, Oh MS. Picrorhiza kurroa prevents memory deficits by inhibiting NLRP3 inflammasome activation and BACE1 expression in 5xFAD mice. Neurotherapeutics. 2020;17:189–99. [DOI] [PubMed] [PMC]

75.

Saresella M, Basilico N, Marventano I, Perego F, La Rosa F, Piancone F, et al. Leishmania infantum infection reduces the amyloid β42-stimulated NLRP3 inflammasome activation. Brain Behav Immun. 2020;88:597–605. [DOI] [PubMed]

76.

Salminen A, Ojala J, Suuronen T, Kaarniranta K, Kauppinen A. Amyloid-beta oligomers set fire to inflammasomes and induce Alzheimer’s pathology. J Cell Mol Med. 2008;12:2255–62. [DOI] [PubMed] [PMC]

77.

Hong Y, Liu Y, Yu D, Wang M, Hou Y. The neuroprotection of progesterone against Aβ-induced NLRP3- caspase-1 inflammasome activation via enhancing autophagy in astrocytes. Int Immunopharmacol. 2019;74:105669. [DOI] [PubMed]

78.

Feng L, Zhang L. Resveratrol suppresses Aβ-induced microglial activation through the TXNIP/TRX/NLRP3 signaling pathway. DNA Cell Biol. 2019;38:874–9. [DOI] [PubMed]

79.

Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, et al. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice. Nature. 2013;493:674–8. [DOI] [PubMed] [PMC]

80.

Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol. 2008;9:857–65. [DOI] [PubMed] [PMC]

81.

Feng J, Wang JX, Du YH, Liu Y, Zhang W, Chen JF, et al. Dihydromyricetin inhibits microglial activation and neuroinflammation by suppressing NLRP3 inflammasome activation in APP/PS1 transgenic mice. CNS Neurosci Ther. 2018;24:1207–18. [DOI] [PubMed] [PMC]

82.

Tejera D, Mercan D, Sanchez-Caro JM, Hanan M, Greenberg D, Soreq H, et al. Systemic inflammation impairs microglial Abeta clearance through NLRP3 inflammasome. EMBO J. 2019;38:e101064. [DOI] [PubMed] [PMC]

83.

Ransohoff RM. A polarizing question: do M1 and M2 microglia exist? Nat Neurosci. 2016;19:987–91. [DOI] [PubMed]

84.

Venegas C, Kumar S, Franklin BS, Dierkes T, Brinkschulte R, Tejera D, et al. Microglia-derived ASC specks cross-seed amyloid-beta in Alzheimer’s disease. Nature. 2017;552:355–61. [DOI] [PubMed]

85.

Lučiūnaitė A, McManus RM, Jankunec M, Rácz I, Dansokho C, Dalgėdienė I, et al. Soluble Abeta oligomers and protofibrils induce NLRP3 inflammasome activation in microglia. J Neurochem. 2020;155:650–61. [DOI] [PubMed]

86.

Santos AN, Ewers M, Minthon L, Simm A, Silber RE, Blennow K, et al. Amyloid-β oligomers in cerebrospinal fluid are associated with cognitive decline in patients with Alzheimer’s disease. J Alzheimer’s Dis. 2012;29:171–6. [DOI] [PubMed]

87.

Mroczko B, Groblewska M, Litman-Zawadzka A, Kornhuber J, Lewczuk P. Amyloid beta oligomers (AbetaOs) in Alzheimer’s disease. J Neural Transm (Vienna). 2018;125:177–91. [DOI] [PubMed]

88.

Parajuli B, Sonobe Y, Horiuchi H, Takeuchi H, Mizuno T, Suzumura A. Oligomeric amyloid beta induces IL-1beta processing via production of ROS: implication in Alzheimer’s disease. Cell Death Dis. 2013;4:e975. [DOI] [PubMed] [PMC]

89.

Couturier J, Stancu IC, Schakman O, Pierrot N, Huaux F, Kienlen-Campard P, et al. Activation of phagocytic activity in astrocytes by reduced expression of the inflammasome component ASC and its implication in a mouse model of Alzheimer disease. J Neuroinflammation. 2016;13:20. [DOI] [PubMed] [PMC]

90.

Brunden KR, Trojanowski JQ, Lee VM. Advances in tau-focused drug discovery for Alzheimer’s disease and related tauopathies. Nat Rev Drug Discov. 2009;8:783–93. [DOI] [PubMed] [PMC]

91.

Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease progress and problems on the road to therapeutics. Science. 2002;297:353–6. [DOI] [PubMed]

92.

Gao Y, Tan L, Yu JT, Tan L. Tau in Alzheimer’s disease: mechanisms and therapeutic strategies. Curr Alzheimer Res. 2018;15:283–300. [DOI] [PubMed]

93.

Stancu IC, Cremers N, Vanrusselt H, Couturier J, Vanoosthuyse A, Kessels S, et al. Aggregated tau activates NLRP3-ASC inflammasome exacerbating exogenously seeded and non-exogenously seeded tau pathology in vivo. Acta Neuropathol. 2019;137:599–617. [DOI] [PubMed] [PMC]

94.

Ising C, Venegas C, Zhang S, Scheiblich H, Schmidt SV, Vieira-Saecker A, et al. NLRP3 inflammasome activation drives tau pathology. Nature. 2019;575:669–73. [DOI] [PubMed] [PMC]

95.

White CS, Lawrence CB, Brough D, Rivers-Auty J. Inflammasomes as therapeutic targets for Alzheimer’s disease. Brain Pathol. 2017;27:223–34. [DOI] [PubMed] [PMC]

96.

Yin J, Zhao F, Chojnacki JE, Fulp J, Klein WL, Zhang S, et al. NLRP3 inflammasome inhibitor ameliorates amyloid pathology in a mouse model of Alzheimer’s disease. Mol Neurobiol. 2018;55:1977–87. [DOI] [PubMed] [PMC]

97.

Dempsey C, Rubio Araiz A, Bryson KJ, Finucane O, Larkin C, Mills EL, et al. Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-beta and cognitive function in APP/PS1 mice. Brain Behav Immun. 2017;61:306–16. [DOI] [PubMed]

98.

Wang CY, Xu Y, Wang X, Guo C, Wang T, Wang ZY. Dl-3-n-butylphthalide inhibits NLRP3 inflammasome and mitigates Alzheimer’s-like pathology via Nrf2-TXNIP-TrX axis. Antioxid Redox Signal. 2019;30:1411–31. [DOI] [PubMed]

99.

Shi JQ, Zhang CC, Sun XL, Cheng XX, Wang JB, Zhang YD, et al. Antimalarial drug artemisinin extenuates amyloidogenesis and neuroinflammation in APPswe/PS1dE9 transgenic mice via inhibition of nuclear factor-kappaB and NLRP3 inflammasome activation. CNS Neurosci Ther. 2013;19:262–8. [DOI] [PubMed] [PMC]

100.

Al Rihani SB, Darakjian LI, Kaddoumi A. Oleocanthal-rich extra-virgin olive oil restores the blood–brain barrier function through NLRP3 inflammasome inhibition simultaneously with autophagy induction in TgSwDI mice. ACS Chem Neurosci. 2019;10:3543–54. [DOI] [PubMed] [PMC]

101.

Wang Y, Guan X, Chen X, Cai Y, Ma Y, Ma J, et al. Choline supplementation ameliorates behavioral deficits and Alzheimer’s disease-like pathology in transgenic APP/PS1 mice. Mol Nutr Food Res. 2019;63:e1801407. [DOI] [PubMed]

102.

Wang HM, Zhang T, Huang JK, Xiang JY, Chen JJ, Fu JL, et al. Edaravone attenuates the proinflammatory response in amyloid-beta-treated microglia by inhibiting NLRP3 inflammasome-mediated IL-1beta secretion. Cell Physiol Biochem. 2017;43:1113–25. [DOI] [PubMed]

103.

Lee CM, Lee DS, Jung WK, Yoo JS, Yim MJ, Choi YH, et al. Benzyl isothiocyanate inhibits inflammasome activation in E. coli LPS-stimulated BV2 cells. Int J Mol Med. 2016;38:912–8. [DOI] [PubMed]

104.

Li Q, Chen L, Liu X, Li X, Cao Y, Bai Y, et al. Pterostilbene inhibits amyloid-β-induced neuroinflammation in a microglia cell line by inactivating the NLRP3/caspase-1 inflammasome pathway. J Cell Biochem. 2018;119:7053–62. [DOI] [PubMed]

105.

La Rosa F, Saresella M, Marventano I, Piancone F, Ripamonti E, Al-Daghri N, et al. Stavudine reduces NLRP3 inflammasome activation and modulates amyloid-β autophagy. J Alzheimers Dis. 2019;72:401–12. [DOI] [PubMed]

106.

Flores J, Noël A, Foveau B, Lynham J, Lecrux C, LeBlanc AC. Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer’s disease mouse model. Nat Commun. 2018;9:3916. [DOI] [PubMed] [PMC]

107.

Shi Y, Wang H, Zheng M, Xu W, Yang Y, Shi F. Ginsenoside Rg3 suppresses the NLRP3 inflammasome activation through inhibition of its assembly. FASEB J. 2020;34:208–21. [DOI] [PubMed]

108.

Kuwar R, Rolfe A, Di L, Xu H, He L, Jiang Y, et al. A novel small molecular NLRP3 inflammasome inhibitor alleviates neuroinflammatory response following traumatic brain injury. J Neuroinflammation. 2019;16:81. [DOI] [PubMed] [PMC]

109.

Tapia-Abellán A, Angosto-Bazarra D, Martínez-Banaclocha H, de Torre-Minguela C, Cerón-Carrasco JP, Pérez-Sánchez H, et al. MCC950 closes the active conformation of NLRP3 to an inactive state. Nat Chem Biol. 2019;15:560–4. [DOI] [PubMed] [PMC]

110.

Coll RC, Robertson AA, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 2015;21:248–55. [DOI] [PubMed] [PMC]

111.

Wen M, Ding L, Zhang L, Zhang T, Teruyoshi Y, Wang Y, et al. Eicosapentaenoic acid-enriched phosphatidylcholine mitigated Aβ1–42-induced neurotoxicity via autophagy-inflammasome pathway. J Agric Food Chem. 2019;67:13767–74. [DOI] [PubMed]

112.

Lee B, Sur B, Park J, Kim SH, Kwon S, Yeom M, et al. Ginsenoside rg3 alleviates lipopolysaccharide-induced learning and memory impairments by anti-inflammatory activity in rats. Biomol Ther (Seoul). 2013;21:381–90. [DOI] [PubMed] [PMC]

113.

Bindu S, Mazumder S, Bandyopadhyay U. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective. Biochem Pharmacol. 2020;180:114147. [DOI] [PubMed] [PMC]

114.

Fan X, Shen W, Wang L, Zhang Y. Efficacy and safety of DL-3-n-butylphthalide in the treatment of poststroke cognitive impairment: a systematic review and meta-analysis. Front Pharmacol. 2022;12:810297. [DOI] [PubMed] [PMC]

115.

Jaiswal MK. Riluzole and edaravone: a tale of two amyotrophic lateral sclerosis drugs. Med Res Rev. 2019;39:733–48. [DOI] [PubMed]