Porphyromonas gingivalis Outer Membrane Vesicles as the Major Driver of and Explanation for Neuropathogenesis, the Cholinergic Hypothesis, Iron Dyshomeostasis, and Salivary Lactoferrin in Alzheimer's Disease
| Autor: | Marc S. Penn, Peter L. Nara, W. Sue T. Griffin, Jan Potempa, Daniel Sindelar |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Iron Cholinergic Agents Virulence Disease Biology cholinergic hypothesis Pathogenesis 03 medical and health sciences Extremophiles 0302 clinical medicine Anti-Infective Agents Alzheimer Disease Bacteroidaceae Infections Humans Saliva Porphyromonas gingivalis Pathogen systemic inflammation Lactoferrin General Neuroscience Brain General Medicine Hypothesis biology.organism_classification Psychiatry and Mental health Clinical Psychology 030104 developmental biology biological extremophile Immunology biology.protein Neuropathogenesis Geriatrics and Gerontology Bacterial outer membrane Alzheimer’s disease 030217 neurology & neurosurgery outer membrane vesicles Bacterial Outer Membrane Proteins dementia |
| Zdroj: | Journal of Alzheimer's Disease |
| ISSN: | 1875-8908 |
| Popis: | Porphyromonas gingivalis (Pg) is a primary oral pathogen in the widespread biofilm-induced “chronic” multi-systems inflammatory disease(s) including Alzheimer’s disease (AD). It is possibly the only second identified unique example of a biological extremophile in the human body. Having a better understanding of the key microbiological and genetic mechanisms of its pathogenesis and disease induction are central to its future diagnosis, treatment, and possible prevention. The published literature around the role of Pg in AD highlights the bacteria’s direct role within the brain to cause disease. The available evidence, although somewhat adopted, does not fully support this as the major process. There are alternative pathogenic/virulence features associated with Pg that have been overlooked and may better explain the pathogenic processes found in the “infection hypothesis” of AD. A better explanation is offered here for the discrepancy in the relatively low amounts of “Pg bacteria” residing in the brain compared to the rather florid amounts and broad distribution of one or more of its major bacterial protein toxins. Related to this, the “Gingipains Hypothesis”, AD-related iron dyshomeostasis, and the early reduced salivary lactoferrin, along with the resurrection of the Cholinergic Hypothesis may now be integrated into one working model. The current paper suggests the highly evolved and developed Type IX secretory cargo system of Pg producing outer membrane vesicles may better explain the observed diseases. Thus it is hoped this paper can provide a unifying model for the sporadic form of AD and guide the direction of research, treatment, and possible prevention. |
| Databáze: | OpenAIRE |
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