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      Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities.

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          Abstract

          Periodontitis, a major inflammatory disease of the oral mucosa, is epidemiologically associated with other chronic inflammation-driven disorders, including cardio-metabolic, neurodegenerative and autoimmune diseases and cancer. Emerging evidence from interventional studies indicates that local treatment of periodontitis ameliorates surrogate markers of comorbid conditions. The potential causal link between periodontitis and its comorbidities is further strengthened by recent experimental animal studies establishing biologically plausible and clinically consistent mechanisms whereby periodontitis could initiate or aggravate a comorbid condition. This multi-faceted 'mechanistic causality' aspect of the link between periodontitis and comorbidities is the focus of this Review. Understanding how certain extra-oral pathologies are affected by disseminated periodontal pathogens and periodontitis-associated systemic inflammation, including adaptation of bone marrow haematopoietic progenitors, may provide new therapeutic options to reduce the risk of periodontitis-associated comorbidities.

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          Most cited references160

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          Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease.

          Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.
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            Inflammation and metabolic disorders.

            Metabolic and immune systems are among the most fundamental requirements for survival. Many metabolic and immune response pathways or nutrient- and pathogen-sensing systems have been evolutionarily conserved throughout species. As a result, immune response and metabolic regulation are highly integrated and the proper function of each is dependent on the other. This interface can be viewed as a central homeostatic mechanism, dysfunction of which can lead to a cluster of chronic metabolic disorders, particularly obesity, type 2 diabetes and cardiovascular disease. Collectively, these diseases constitute the greatest current threat to global human health and welfare.
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              Alzheimer Disease: An Update on Pathobiology and Treatment Strategies

              Alzheimer disease (AD) is a heterogeneous disease with a complex pathobiology. The presence of extracellular amyloid-β deposition as neuritic plaques and intracellular accumulation of hyperphosphorylated tau as neurofibrillary tangles remain the primary neuropathologic criteria for AD diagnosis. However, a number of recent fundamental discoveries highlight important pathological roles for other critical cellular and molecular processes. Despite this, no disease modifying treatment currently exists and numerous phase 3 clinical trials have failed to demonstrate benefit. We review here recent advances in our understanding of AD pathobiology and discuss current treatment strategies, highlighting recent clinical trials and opportunities for developing future disease modifying therapies.
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                Author and article information

                Journal
                Nat Rev Immunol
                Nature reviews. Immunology
                Springer Science and Business Media LLC
                1474-1741
                1474-1733
                July 2021
                : 21
                : 7
                Affiliations
                [1 ] Department of Basic and Translational Sciences, Penn Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA. geoh@upenn.edu.
                [2 ] Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
                Article
                10.1038/s41577-020-00488-6
                10.1038/s41577-020-00488-6
                7841384
                33510490
                bc3cfe64-87e2-4007-9031-99e13c1e9c04
                History

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