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Review

Targeting TLR2/TLR4 Pathways in Periodontitis: Molecular Insights and Emerging Aptamer-Based Therapeutic Strategies

Muhammad Aiman Bin Azizul ORCID ,  Yun Han Ng ORCID ,  Nydia Lynn Yong Shu Thiin ORCID ,  Nur Alia Binti Othman ORCID ,  Fong Fong Liew ORCID
    Received: 18 May 2026; Revised: 8 June 2026; Accepted: 4 August 2026; Published: 20 August 2026

    Abstract

    Periodontitis is a chronic inflammatory disease of the gingival and periodontal tissues, primarily initiated by bacterial accumulation and driven by an excessive host immune response. This persistent inflammatory condition promotes periodontal tissue degradation through the activation of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) signalling pathways, leading to the production of pro-inflammatory mediators, including interleukin-6, interleukin-8 and tumour necrosis factor-alpha. These mediators alter the local inflammatory microenvironment, perpetuate immune activation and contribute to progressive periodontal tissue destruction. This review summarises the roles of TLR2- and TLR4-associated genes, proteins and microRNAs in the pathogenesis of periodontitis, based on reported research findings, STRING protein–protein interaction network analysis, GO/Reactome enrichment analysis and profiling. The study also explores the potential roles of antibodies and aptamers in suppressing inflammation and promoting wound healing. Although antibodies exhibit high target specificity, their complex manufacturing processes, higher costs and potential immunogenicity may limit their clinical applicability compared with aptamers. Aptamers, in contrast, are relatively stable, cost-effective and generally non-immunogenic, making them promising molecular tools for targeted therapeutic intervention. Based on the reviewed findings, aptamers may be further explored as potential therapeutic agents for regulating intracellular signalling pathways associated with TLR2- and TLR4-mediated inflammation. Overall, this review highlights the relationship between molecular mechanisms and therapeutic innovation in periodontitis, particularly through TLR2- and TLR4-associated pathways. It also emphasises the relevance of molecular network analysis, computer-assisted simulation technologies and precision medicine approaches in advancing therapeutic strategies for chronic inflammatory disorders.

    Keywords

    References

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