Oral disease-associated proteins implicated in neuronal disorders: Emerging roles in diagnosis and treatment

Oral health plays a crucial role in maintaining cognitive functions, reflecting a complex interplay between the oral cavity and brain health. Emerging evidence indicates that various oral disease-associated protein molecules are implicated in the pathogenesis of diverse neuronal disorders, including neurodegenerative diseases. This review comprehensively summarizes oral disease-related protein molecules involved in several neuronal disorders, including Alzheimer's disease, Parkinson's disease, neurodegeneration, neuroinflammation, dementia, cognitive decline, and brain fog in two different contexts. Firstly, it describes protein molecules under the classical oral disease condition [Aβ42, total-Tau, phosphorylated-Tau, α-synuclein, DJ-1, lactoferrin, MMP-2/8/9, IL-6, IL-1β, TNF-α, CRP, S100A8, S100A9, S100B, RAGE, LCN2, cathepsin B/L, HSP70/90, NfL, CXCL2/8, C3/4, defensins (α and β), and lysozyme]. Secondly, it explains in COVID-19 context [ACE2, TMPRSS2, furin-1, NRP1, spike, T1R, and T2R]. The review explores oral proteins implicated in neuronal disorders, highlighting their roles in activating inflammatory pathways, contributing to memory impairment, and mediating taste dysfunction in the context of COVID-19. Furthermore, the review delineates the mechanisms underlying the oral-brain axis, highlighting the roles of systemic inflammation, microbial interactions, and blood-brain barrier dysfunction in mediating these effects. It also highlights the innovative diagnostic potential of oral disease-associated proteins as non-invasive biomarkers for early detection and monitoring of neuronal disorders in both classical and COVID-19 contexts. In addition, the emerging therapeutic significance of these proteins is discussed, emphasizing their potential as molecular targets for the prevention and treatment of neurological diseases. Understanding oral disease-associated protein molecules provides novel insights into early diagnosis and progression of neuronal disorders.