Correlation between oral disease and neurodegenerative disorders: Role of biological proteins for the modulation of oral-brain axis and gut-brain axis

Abstract

Biological proteins play a crucial role at the intersection of oral health and neuroscience, offering promising opportunities for improved diagnosis, prevention, and treatment. This review highlights the molecular, inflammatory, and biochemical pathways linking oral diseases, particularly periodontal disease and microbial dysbiosis, with neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Key inflammatory, neuroprotective, and tissue-repair proteins play a crucial role in maintaining both oral integrity and neural function. Advances in proteomics and molecular imaging have clarified how protein misfolding, aggregation, and immune responses drive neuroinflammation and cognitive decline. Emerging therapies include protein-based biomaterials, such as hydrogels, nanocarriers, and protein–polymer hybrids, for delivering neuroprotective and regenerative agents through oral and nasal routes. Early diagnosis is being transformed by salivary proteomics and transcriptomics, enabling non-invasive detection of neurodegenerative biomarkers. Host-defense peptides and antimicrobial proteins also show promise in controlling oral infections that may exacerbate brain inflammation. Integrating oral biology, biomaterials science, and neuroscience is accelerating clinical translation through the development of innovative scaffolds and smart delivery systems. Despite challenges in biomarker validation and clinical application, advances in artificial intelligence, bioinformatics, and protein engineering are driving the future of personalized regenerative and preventive medicine. Overall, biological proteins provide a critical molecular link between oral and neural health, paving the way for novel non-invasive diagnostic and therapeutic strategies.