# Emerging Role of the NLRP3 Inflammasome in the Onset of Oral Diseases and Its Potential as a Therapeutic Target

## TL;DR

The NLRP3 inflammasome plays a key role in oral diseases and could be a new target for treatments to reduce inflammation and tissue damage.

## Contribution

This review provides an updated analysis of NLRP3's role in oral diseases and highlights its potential as a therapeutic target.

## Key findings

- NLRP3 inflammasome activation contributes to inflammation and tissue destruction in oral diseases.
- Preclinical studies show that NLRP3 inhibitors and natural compounds can reduce tissue damage.
- Translational research is needed to move NLRP3-targeted therapies into clinical practice.

## Abstract

Growing evidence suggests that persistent oral infectious diseases (OIDs) contribute to systemic disease, highlighting the importance of understanding their pathogenic mechanisms. Conventional dental treatments, primarily mechanical debridement, surgical intervention, or antimicrobial therapy, often struggle to fully control inflammation or prevent progressive tissue destruction. The nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome is a key regulator of innate immunity, mediating the maturation of proinflammatory cytokines (IL-1β and IL-18) and the pyroptosis-inducing protein gasdermin D. Dysregulated or excessive activation of NLRP3 contributes to the initiation and progression of major oral diseases, including periodontitis, peri-implantitis, pulpitis, and oral mucosal inflammation. Despite growing interest in NLRP3, comprehensive and up-to-date reviews integrating its pathogenic mechanisms and therapeutic potential remain limited. This review summarizes current and past evidence on the role of the NLRP3 inflammasome in oral disease development, highlights emerging pharmacological strategies, and outlines future research directions. Existing studies demonstrate that microbial components and danger signals from injured tissues activate NLRP3, thereby amplifying inflammation, tissue degradation, and bone resorption. Preclinical studies indicate that inflammasome inhibitors and several natural compounds reduce tissue damage; however, their clinical translation remains limited. These findings emphasize the need for deeper understanding of NLRP3-mediated pathways, with translational and clinical research offering promising therapeutic opportunities for oral diseases.