Table III.
Drugs that prevent and treat AD through the NLRP3 signaling pathway.
| First author, year | Compound and original source | In vivo model | In vitro model | Dose and drug administration time | Targets | Signaling pathways | (Refs.) |
|---|---|---|---|---|---|---|---|
| Lonnemann et al, 2020 | OLT1177/- | APP/PS1Δ E9 mice | LPS-induced primary microglia |
In vivo: 3.75, 7.5 g/kg; 3 months In vitro: 5, 10 μM; 24 h |
↓: CD68, TNF-α, IL-1β, IL-6, NLRP3, Iba-1, the number of plaques | NLRP3 | (198) |
| Dempsey et al, 2017 | MCC950/- | APP/PS1 double transgenic AD mice | LPS+Aβ-induced primary microglia |
In vivo: 10 mg/kg; 3 months In vitro: 100 nM; 5 h |
↓: IL-1β, LDH, caspase 1, inflammasome assembly, Aβ, CD11b, CD68 | NLRP3 | (201) |
| Fekete et al, 2019 | AβO-induced AD rats APPNL-F/NL-F mice | - | In vivo: 1 μg; 4 weeks | ↓:Iba1, Cd11b, Cd68, Cd80, Cd86, RT1-EC2, Ccl2, Cxcl10, C3, Cfb, NLR3, Il1b, Tnf, Il12b, Nos2, Cx3cl1, Cd200, Cd22, Cx3cr1, Cd200r, Cd45 ↑: Scn1,IL-10 |
- | (202) | |
| Kuwar et al, 2021 | JC124/- | APP/PS1 double transgenic mice with AD | - | In vivo: 50, 100 mg/kg; 3 months | ↓: Aβ, Iba1, HMGB1, GFAP, D1 ↑: generation and survival of new neurons, pre-synaptic proteins, synapsin-1, synaptophysin |
NLRP3 | (203) |
| Zhang et al, 2021 | GB/Ginkgo biloba | - | Aβ1-42-induced BV2 cells | In vitro: 100 μM; 2 h | ↓: Cytotoxic, NLRP3, caspase-1, IL-1β, Aβ, CD16/32, iNOS ↑:CD206, Arg-1, CD206 |
NLRP3 | (204) |
| Zhang et al, 2015 | PF/Paeonia lactiflora Pall | APP/PS1 double transgenic mice with AD | - | In vivo: 5 mg/kg; 4 weeks | ↓: Aβ, GFAP, CD11b, TNF-α, IL-1β, p-NF-κB p65, p-I-κBa, NLRP3, caspase-1 p20 ↑: IL-10, IL-4, p-AKT, p-GSK3β-pSer9 |
NLRP3 | (207) |
| Kong et al, 2020 | A419259/- | LPS-induced C57BL/6J mice | LPS-induced primary microglia |
In vivo: 30 mg/kg; 3 h In vitro: 1 μM; 1 h |
↓: Caspase 1, IL-1β, ASC, the interaction between HCK and NLRP3, IL-6, IL-10 | NLRP3 | (211) |
| Cui et al, 2020 | TAK-242/- | APP/PS1 double transgenic mice with AD | Aβ-induced BV2 cells |
In vivo: 2 mg/kg; 28 days In vitro: 100 nM; 8 h |
↓: TLR4, CD11b, amoeboid microglial cells, iNOS, TNFα, MyD88, NF-κB p65, NLRP3, Bax, iNOS ↑: TREM-2,Arg-1 |
TLR4/MyD88/NF-κB/NLRP3 | (212) |
| Liu et al, 2020 | CLI-095/- | - | LPS + Aβ1−42-induced BV2 cells and primary microglia | In vitro: 1 μM; 2 h | ↓: NLRP3, ASC, caspase1 p10, IL-1β, Iba-1, IL-1β, TNF-α, iNOS, Cox-2 | TLR4/NLRP3 | (214) |
| Li et al, 2018 | Pterostilbene/- | - | Aβ1–42-induced BV2 cells | In vitro: 5, 10 μM; 24 h | ↓: NO, iNOS, IL-6, IL-1β, TNF-α, NLRP3, caspase1 | NLRP3/caspase1 | (216) |
| Wang et al, 2021 | LDS/- | - | LPS-induced BV2 cells | In vitro: 400, 200, 100 μg/ml; 12 h | ↓: iNOS, COX-2, NO, IL-1β, TNFα, IL-6, NLRP3, TLR4, MyD88, caspase1, Iba1, Tau | NLRP3/caspase1 | (217) |
| Liu et al, 2022 | PPSR/- | - | LPS+Aβ42-induced primary microglia | In vitro: transfection; 6 h | ↓: ROCK2, IL-1β, NLRP3, procaspase-1, caspase-1 | NLRP3/caspase1 | (219) |
| Han et al, 2021 | Sulfa-4 and sulfa-22/- | APP/PS1 double transgenic mice with AD | LPS+nigericin-induced BV2 cells |
In vivo: 5 mg/kg; 14 days In vitro: Sulfa-4 (IC50 of 3 μM); 4 h Sulfa-22 (IC50 of 5 μM); 4 h |
↓: LDH, PI uptake rate, p30-GSDMD, IL-18, IL-1β, TNF-α, NLRP3, Caspase-1, IBA-1, CD11c | NLRP3/caspase1/GSDMD | (221) |
| Kim et al, 2021 | Donepezil/- | LPS-induced C57BL6/J mice 5XFAD mice APP/PS1 double transgenic mice with AD | LPS-induced BV2 cells |
In vivo: 1 mpk; 3 days/2 weeks In vitro: 50 μM; 23.5 h |
↓: COX-2, IL-1β, IL-6, iNOS, ROS, p-AKTser473, p-AKTT308, p-ERK, p-P38 T180/Y18, p-NF-kBSer536, p-STAT3 Ser727, NLRP3, pro-IL-1β, IL-1β, Iba-1,GFAP | MAPK/NLRP3/STAT3 | (225) |
| Kim et al, 2014 | AβO-induced mice with AD | AβO1-42-induced BV2 cells, rat primary microglia and primary hippocampal cells |
In vivo: 2 mg/kg; 5 days In vitro: 0.1, 1 μM; 24 h |
↓: NO, TNF-α, IL-1β, PGE2, iNOS, COX-2, p38 MAPK, NF-κB p65 translocation to nucleus, Mac-1, GFAP ↑:cell viability |
MAPK and NF-κB signaling | (226) | |
| Gao et al, 2020 | TSG/Polygoni multiflori Radix | - | LPS-induced BV2 cells | In vitro: 1, 10 μM; 10, 100 nM; 24 h | ↓: TNF-α, IL-1β, IL-18, iNOS, COX-2, P62, p-Drp1(S637), MFF, NLRP3, procaspase-1, cleaved caspase-1, IL-1β/IL-1F2, IL-3, G-CSF, GM-CSF, IL-5, CCL5/RANTES, CCL4/MIP1β, IL-2, IL-4, IL-10, IFN-γ, CCL5/RANTES, CCL4/MIP1β, IL-2 ↑: LC3-II/LC3-I, Parkin, PINK1, Beclin1, Drp1, Mfn2 |
AMPK related PINK1/Parkin/NLRP3 | (229) |
| Zhang et al, 2019 | Fasudil and Y27632/- | - | LPS-induced BV2 cells | In vitro: Fasudil (50 μM), Y27632 (10 μM); 24 h | ↓: Cell migration, NLRP3, pro-CASP1, pro-IL-1β,IL-1β | RhoA/ROCK/NLRP3 | (238) |
AD, Alzheimer's disease; OLT1177, dapansutrile; GB, ginkgolide B; PF, paeoniflorin; TAK-242, ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl) sulfamoyl] cyclohex-1-ene-1-carboxylate); LDS, lignin-amides from Datura metel seeds; PPSR, PEG-PEI/siROCK2; TSG, tetrahydroxy stilbene glycoside; Aβ, amyloid β; APP/PS1, amyloid-β protein/presenilin-1; 5XFAD, 5X familial Alzheimer's disease; AMPK, Adenosine 5′-monophosphate (AMP)-activated protein kinase; ASC, apoptosis-associated speck-like protein; COX-2, cyclooxygenase-2; ERK, extracellular signal-regulated kinases; GFAP, glial fibrillary acidic protein; GSDMD, gasdermin D; HCK, Hematopoietic cell kinase; IL, interleukin; iNOS, inducible nitric oxide synthase; IFN-γ, interferon-γ; LPS, lipopolysaccharide; MyD88, myeloid differentiation factor 88; MAPK, mitogen-activated protein kinase; NLRP3, NOD-like receptor thermal protein domain associated protein 3; NO, nitric oxide; PINK1, PTEN-induced kinase 1; ROS, reactive oxygen species; ROCK, Rho-dependent coiled-coil kinase; TLRs, Toll-like receptors; p-phosphorylated; NF-κB, nuclear factor-kappa-B; Iba-1, ionized calcium binding adaptor molecule 1; STAT3, signal transducers and activators of transcription 3; AP-1, activator protein 1; PGE2, prostaglandin E2.