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Numerous epithelial cells and sometimes leukocytes release AMPs as their first line of defense. AMPs encompass cationic histatins, defensins, and cathelicidin to encounter oral pathogens with minimal resistance. However, their concentrations are significantly below the effective levels and AMPs are unstable under physiological conditions due to proteolysis, acid hydrolysis, and salt effects. In parallel to a search for more effective AMPs from natural sources, considerable efforts have focused on synthetic stable and low-cytotoxicy AMPs with significant activities against microorganisms. Using natural AMP templates, various attempts have been used to synthesize sAMPs with different charges, hydrophobicity, chain length, amino acid sequence, and amphipathicity. Thus far, sAMPs have been designed to target Streptococcus mutans and other common oral pathogens. Apart from sAMPs with antifungal activities against Candida albicans , future endeavors should focus on sAMPs with capabilities to promote remineralization and antibacterial adhesion. Delivery systems using nanomaterials and biomolecules are promising to stabilize, reduce cytotoxicity, and improve the antimicrobial activities of AMPs against oral pathogens. Nanostructured AMPs will soon become a viable alternative to antibiotics due to their antimicrobial mechanisms, broad-spectrum antimicrobial activity, low drug residue, and ease of synthesis and modification.

Important Roles and Potential Uses of Natural and Synthetic Antimicrobial Peptides (AMPs) in Oral Diseases: Cavity, Periodontal Disease, and Thrush