NLRP3/1-mediated pyroptosis: beneficial clues for the development of novel therapies for Alzheimer's disease

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis, which is a lytic, inflammatory form of cell death. There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3 (NLRP3) inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer's disease. In this review, we summarize the possible pathogenic mechanisms of Alzheimer's disease, focusing on neuroinflammation. We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer's disease. Finally, we examine the neuroprotective activity of small-molecule inhibitors, endogenous inhibitor proteins, microRNAs, and natural bioactive molecules that target NLRP3 and NLRP1, based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer's disease.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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