TABLE 1.
The compounds or extractions targeting NLRP3 inflammasome pathways in AD.
| Compounds or extractions | Mechanism | Cell or animal model | References |
|---|---|---|---|
| IL-1 inhibitors | |||
| anakinra | IL-1 receptor antagonist | 3xTg-AD transgenic mice | Kitazawa et al. (2011) |
| IL-1 receptor antagonist | AD amyloidosis rat model | Qi et al. (2018), Batista et al. (2021) | |
| rilonacept | IL-1inducible receptor | — | Giancane et al. (2016) |
| canakinumab | Antibody targeting IL-1β | — | Giancane et al. (2016) |
| NLRP3 inhibitors | |||
| Glyburide | ATP sensible K+ channels, downstream of the P2X7 receptor | — | Lamkanfi et al. (2009) |
| JC124 | Inhibits the NLRP3 inflammasome and the activation of caspase-1 | APP/PS1 or CRND8 APP transgenic mice | Fulp et al. (2018), Yin et al. (2018), Kuwar et al. (2021) |
| Oridonin | Covalent bond with NLRP3 in NACHT domain to block the interaction between NLRP3 and NEK7 | Aβ1-42 induced AD mice | Wang et al. (2014), Wang et al. (2016), He et al. (2018) |
| CY-09 | Binds to the ATP binding motif of the NLRP3 NACHT domain to inhibit NLRP3 ATPase activity | — | Jiang et al. (2017) |
| MCC950 | Walker B motif interaction and inhibition of ATP hydrolysis, selective inhibitor of NLRP3 | APP/PS1 AD, Long evans rats, SAMP8 mouse | Qi et al. (2018), Coll et al. (2019), Fekete et al. (2019), Li et al., 2020b) |
| Selective inhibitor of NLRP3 | Microglia induced by Aβ aggregates | Luciunaite et al. (2020) | |
| OLT1177 | Binds to NLRP3 to inhibit its ATPase activity | APP/PS1 mice | Marchetti et al. (2018), Lonnemann et al. (2020) |
| Tranilast | Directly binds to the NACHT of NLRP3 and blocks NLRP3 oligomerization | — | Huang et al. (2018) |
| BAY 11–7082 | Inhibits NLRP3 ATPase activity | APP 23 mice, BV2 cells | Ruan et al. (2019) |
| Parthenolide | Inhibits NLRP3 ATPase activity and caspase-1 | Primary glial cells | Ou et al. (2020) |
| MNS | Inhibits the activity of NLRP3 ATPase through binding to the LRR and NACHT domains | — | He et al. (2014) |
| ASC inhibitors | |||
| BHB | Prevents K+ efflux and reduces ASC oligomerization and speck formation | 5xFAD mouse | Youm et al. (2015), Shippy et al. (2020) |
| Improves the cognitive function | AD patients | Ota et al. (2019) | |
| Caspase-1 inhibitors | |||
| VX-765 | Inhibits caspase-1 | AD J20 mouse | Flores et al. (2018), Flores et al. (2020) |
| Ac-YVAD-CMK | Inhibits caspase-1 | APP/PS1 AD mice | Gu et al. (2021) |
| Plant-derived compounds | |||
| Resveratrol | Inhibits TXNIP/TRX/NLRP3 signaling pathway | BV-2 cells | Feng and Zhang, (2019) |
| Inhibits NF-κB/IL-1β/NLRP3 signaling pathway | AD mouse model induced by Aβ1-42 | Qi et al. (2019) | |
| Pterostilbene | Inhibits the NLRP3/caspase-1 pathway | Microglia induced by Aβ1-42 | Li et al. (2018) |
| SFN | Inhibits the NLRP3 inflammasome | N9 microglial cells | Tufekci et al. (2021) |
| GB | Inhibits NLRP3 activation and promotes microglia M2 polarization | BV2 microglial cells induced by Aβ1-42 | Zhang et al. (2021b) |
| ABPPκ | Inhibits the expression of NLRP3, cleaved caspase-1, and ASC | BV2 microglia, Aβ oligomers-injected mice | Ge et al. (2021) |
| Chinese herbal medicines | |||
| PK | Inhibits the NLRP3 inflammasome | 5xFAD mouse | Kim et al. (2020) |
| DHM | Inhibits the NLRP3 inflammasome | APP/PS1 mice | Feng et al. (2018) |
| NSAIDs | |||
| IND | Reduces the expression of IL-1β and caspase-1 | AD rats induced by streptozotocin | Karkhah et al. (2021) |
| MicroRNAs | Directly or indirectly inhibits the expression of NLRP3 | Glial cells, AD mice, and AD patients | Han et al. (2020), Feng et al. (2021), Wan et al. (2021) |
| Autophagy activators | |||
| A-68930 | Enhances the degradation of NLRP3 inflammasome by activating the AMPK/autophagy signaling pathway | BV2 cells, AD mice induced by Aβ1-42 | Cheng et al. (2020) |
| PG | Inhibits the activation of NLRP3-caspase-1 via enhancing the autophagy | Astrocytes | Hong et al. (2019) |
| EGb 761 | Down-regulates the level of NLRP3 protein, reduces the activation of IL-1β and caspase-1 via autophagy | TgCRND8 AD model | Liu et al. (2015) |
| Mitophagy activators | |||
| TSG | Prevents NLRP3 inflammation through mitophagy | APP/PS1 mice, BV2/N2a/SH-SY5Y cells | Gao et al. (2020) |
| Qu | Inhibits NLRP3 inflammation through mitophagy | Primary microglia, BV2 cells | Han et al. (2021) |
| ROS and NF-κB inhibitors | |||
| α-lipoic acid | Inhibits NLRP3 via the NF-κB signaling pathway | BV-2 microglial cells | Kim et al. (2019) |
| Edaravone | Reduces the production of mtROS, and inhibits the activation of NLRP3 | Aβ-treated microglia | Wang et al. (2017) |
| Donepezil | Down-regulates NLRP3 and pro-IL-1β mRNA levels by inhibiting NF-κB/STAT3 phosphorylation | BV2 microglial cells, 5xFAD mice | Kim et al. (2021) |