Table 1.
The therapies targeting NLRP3 Inflammasome in AD.
| Therapeutic Strategy | Mechanism | Effect |
|---|---|---|
| Targeting IL-1β (Anakinra) | Modulates IL-1β activity by using IL-1 receptor antagonists, monoclonal antibodies, and decoy receptors. | Reduce IL-1β, improve cognitive function, and alleviate neuroinflammation. |
| Ginkgolide B (GB) | Inhibits NLRP3 inflammasome activation and reduces neuroinflammation. | GB reduces Aβ-induced pathology, enhances M2 microglia, suppresses pro-inflammatory cytokines, and improves cognitive function. |
| Sulforaphane (SFN) | Inhibits NLRP3 inflammasome activation via NF-κB downregulation and reduces pyroptosis. | SFN diminishes IL-1β/IL-18 release, inhibits caspase-1, and reduces NLRP3 overexpression in LPS-activated microglia. Shows anti-inflammatory and neuroprotective effects. |
| Dapansutrile (OLT1177) | Selectively inhibits NLRP3 inflammasome by blocking ATPase function and inflammasome activation. | OLT1177 improves cognitive function, reduces microglial activation, and lowers Aβ plaque accumulation in AD mouse models. Favorable pharmacokinetic properties. |
| MCC950 | Selectively inhibits NLRP3 inflammasome via NACHT domain targeting. | MCC950 inhibits inflammasome activation by Aβ/tau, reducing IL-1β release and preventing neuronal toxicity in AD models. |
| Ketone Bodies | Ketogenic diets and ketone bodies (e.g., β-hydroxybutyrate) inhibit NLRP3 inflammasome activation and reduce Aβ buildup. | β-Hydroxybutyrate inhibits NLRP3 inflammasome, reduces Aβ internalization, and mitigates AD progression. 2-DG enhances bioenergetic capacity and promotes Aβ clearance. |
| Other Strategies | NSAIDs, microRNAs, autophagy, mitophagy, and botanical extracts modulate NLRP3 inflammasome activity. | Indomethacin, miR-138–5p, miR-223, Quercetin, Ginkgo biloba, and others reduce NLRP3 activation, improving cognition and reducing neuroinflammation. |
| New Therapies | Targets autophagy, mitophagy, and inflammasome activation. | Cornuside, Thonningianin A, and Eriodictyol inhibit NLRP3 inflammasome activation, promote mitophagic flux, and improve cognitive function in AD models. |