Table 2.
The main NLRP3/cas-1 inhibitors to counteract inflammation in PD models
| Name | Activity | Model/Study | Effects |
|---|---|---|---|
| Direct NLRP3 inhibitors | |||
| MCC950 (CP-456,773) | Small molecule NLRP3 inhibitor | Cultured microglia; Murine PD model [95] | Neuroprotective effects on dopaminergic nigrostriatal neurons; inhibition of release of IL-1β and caspase 1 |
| Kaempferol | NLRP3 inhibitor | Murine PD model [96] | Decreases neuronal apoptosis and production of pro-inflammatory cytokines; increases mRNA and protein expression of tyrosine hydroxylase |
| Oridonin | NLRP3 inhibitor | Cultured cells [97] | Decreases production of ROS and pro-inflammatory cytokines |
| Fingolimod (FTY-720) | NLRP3 inhibitor | Cultured microglia; Murine PD model [98] | Decreases dopaminergic neurodegeneration |
| AZ11645373 | NLRP3 inhibitor, P2X7 receptor antagonist | Murine PD model [99] | Inhibits release of IL-1β |
| Celastrol | NLRP3 inhibitor | Murine PD model [100] | Relieves motor deficits and nigrostriatal dopamine degeneration |
| Inhibitors of NLRP3-mediated pathways | |||
| Dapagliflozin | NF-κB pathway inhibitor | Murine PD model [101] | Suppresses neuroinflammation by decreasing ROS production; decreases TNF-α levels |
| Lenalidomide | NF-κB pathway inhibitor | Murine PD model [102, 103] | Decreased pro-inflammatory cytokine production; suppresses levels of phosphorylated NF-κB; reduces microglial activation; improves motor and behavioral symptoms |
| Triptolide | NF-κB pathway inhibitor (via miRNA 155-5p/SHIP1 pathway) | Murine PD model [104] | Decreases microglial activation and production of pro-inflammatory cytokines |
| Juglanin | TLR4 and NF-κB pathway inhibitor | Murine PD model [105] | Decreases production of IL-1β, IL-18, TNF-α, and COX-2 |
| Calycosin | TLR/NF-κB and MAPK pathways inhibitor | Cultured microglial cells; murine PD model [106, 107] | Decreases production of pro-inflammatory cytokines; alleviates behavioral symptoms |
| Diosgenin | TLR/NF-κB pathway inhibitor | Cultured microglial cells; murine PD model [108] | Decreases ROS production; decreases expression of TLR2, TLR4 and NF-κB; decreases mRNA levels of pro-inflammatory cytokines |
| Isobavachalcone | NF-κB pathway inhibitor | Cultured microglial cells; murine PD model [109] | Decreases production of pro-inflammatory cytokines and microglial activation |
| Apocynin | NADPH oxidase inhibitor | Murine PD model [110] | Decreases ROS production; prevents learning deficits |
| Diphenyleneiodonium | NADPH oxidase inhibitor | Murine PD model [111] | Decreases expression of pro-inflammatory cytokine and ROS genes |
| miRNA-7 | NLRP3 inhibitor | Cultured neuronal and microglial cells; murine PD model [112] | Neuroprotective effects on dopaminergic neurons; inhibition of NLRP3 activation |
| miRNA-30e | NLRP3 inhibitor | Cultured neuronal and microglial cells; murine PD model [113] | Inhibits mRNA and protein NLRP3 synthesis; decreases production of pro-inflammatory cytokines |
| Caspase-1 inhibitors | |||
| Necrostatins | Cas-1 inhibitor | Cultured microglial cells [114] | Increases neuroprotection on dopaminergic neurons |