Porphyromonas gingivalis-Induced Neuroinflammation in Alzheimer’s Disease

Olsen, Ingar

doi:10.3389/fnins.2021.691016

Cited by 18 publications

(14 citation statements)

References 49 publications

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“…Instead of the application of antibiotics that have no impact against pathogenic bacterial bio ilms, some natural products emerge as potent factors interfering with QS and thus bio ilm formation [24]. P.gingivalis is one bacterium found in oral bio ilms that are correlated with many burden disorders like AD [25]. Therefore, upon targeting the QS pathway and preventing bio ilm formation, a huge number of in licted populations will bene it especially if the cure is of natural origin.…”

Section: Resultsmentioning

confidence: 99%

In silico disrupting quorum sensing of porphyromonas gingivalis via essential oils and coumarin derivatives

Al-Madhagi¹,

Samman²

2022

Ann Proteom Bioinform

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The emergence of porphyromonas gingivalis biofilm is a hallmark of risky burden diseases including Alzheimer's disease and atherosclerosis. The current study aims to screen some natural essential oil compounds and coumarin derivatives to interfere with quorum sensing of the bacterium and thus biofilm formation. A total of 20 ligands (10 essential oil molecules and 10 coumarin derivatives) were docked to P.gingivalis heme-binding protein HmuY using UCSF Chimera built-in AutoDock interface. Alongside, ADMET properties were also predicted via ADMETsar 2.0 and ProTox-II webservers. All of the selected ligands had higher free energy values than the reference inhibitor MES and native coumarin as well. Moreover, ADME parameters are in good agreement with Lipinski's rule of five. Nevertheless, the best molecules with top binding energy exhibited slight immunogenicity as well as carcinogenicity issues requiring in vitro confirmation. In conclusion, the tested ligands had better efficacy against P.gingivalis quorum sensing and biofilm.

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Section: Resultsmentioning

confidence: 99%

In silico disrupting quorum sensing of porphyromonas gingivalis via essential oils and coumarin derivatives

Al-Madhagi¹,

Samman²

2022

Ann Proteom Bioinform

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“…Inflammasome mutations can lead to inappropriate caspase-1 activation, which is associated with autoinflammatory syndromes [ 80 ]. Moreover, caspase-1 is involved in the pathogenesis of several diseases, including periodontal disease [ 4 ], Alzheimer’s disease [ 81 , 82 ], cardiovascular disease [ 83 ], rheumatoid arthritis [ 84 ], endometriosis [ 70 ], and Crohn’s disease [ 85 ], all of which are characterised by cell death and inflammation. Caspase-1 deficiency or inhibition protects against cell death, inflammation, and tissue dysfunction, associated with these diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the inflammasomes were also found to be the link among endometriosis, atherosclerosis, periodic fever syndromes, vitiligo, Crohn’s disease, gout, asbestosis, silicosis, and periodontitis [ 70 ]. In addition, neuroinflammation with pyroptosis is recognised as a pathological factor in Alzheimer’s disease [ 81 , 82 ]. Such associations give clues regarding the pathogenic mechanisms involving inflammasomes that are crucial for developing therapies or even for preventing such diseases [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Pyroptosis-Mediated Periodontal Disease

Sordi

Magini

Panahipour

et al. 2021

IJMS

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Pyroptosis is a caspase-dependent process relevant to the understanding of beneficial host responses and medical conditions for which inflammation is central to the pathophysiology of the disease. Pyroptosis has been recently suggested as one of the pathways of exacerbated inflammation of periodontal tissues. Hence, this focused review aims to discuss pyroptosis as a pathological mechanism in the cause of periodontitis. The included articles presented similarities regarding methods, type of cells applied, and cell stimulation, as the outcomes also point to the same direction considering the cellular events. The collected data indicate that virulence factors present in the diseased periodontal tissues initiate the inflammasome route of tissue destruction with caspase activation, cleavage of gasdermin D, and secretion of interleukins IL-1β and IL-18. Consequently, removing periopathogens’ virulence factors, triggering pyroptosis, is a potential strategy to combat periodontal disease and regain tissue homeostasis.

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“…Both periodontopathogenic bacteria and their products can enter the bloodstream, promoting the expression of inflammatory mediators that can damage other organs, including the brain. Interestingly, gingipains are proteases that generate pathogenicity factors such as Arg-gingipain (Rgp) and Lys-gingipain (Kgp), which can damage tau [30,118]. In this regard, atuzaginstat (COR388) is an inhibitor of gingipains, which is being tested in a phase II/III clinical study for AD treatment (NCT03823404) (Fig.…”

Section: Immunity and Inflammation As Therapeutic Targetsmentioning

confidence: 99%

“…Specifically, we describe drugs under clinical study targeting Aβ, tau, neuroinflammation and other risk factors, which may serve in future therapeutic approaches (Table 1, Ref. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]).…”

Section: Introductionmentioning

confidence: 99%

Impact of New Drugs for Therapeutic Intervention in Alzheimer’s Disease

Olloquequi¹,

Ettcheto²,

Cano³

et al. 2022

Front. Biosci. (Landmark Ed)

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The increases in population ageing and growth are leading to a boosting in the number of people living with dementia, Alzheimer's disease (AD) being the most common cause. In spite of decades of intensive research, no cure for AD has been found yet. However, some treatments that may change disease progression and help control symptoms have been proposed. Beyond the classical hypotheses of AD etiopathogenesis, i.e., amyloid beta peptide (Aβ) accumulation and tau hyperphosphorylation, a trend in attributing a key role to other molecular mechanisms is prompting the study of different therapeutic targets. Hence, drugs designed to modulate inflammation, insulin resistance, synapses, neurogenesis, cardiovascular factors and dysbiosis are shaping a new horizon in AD treatment. Within this frame, an increase in the number of candidate drugs for disease modification treatments is expected, as well as a focus on potential combinatory multidrug strategies.The present review summarizes the latest advances in drugs targeting Aβ and tau as major contributors to AD pathophysiology. In addition, it introduces the most important drugs in clinical studies targeting alternative mechanisms thought to be involved in AD's neurodegenerative process.

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Porphyromonas gingivalis-Induced Neuroinflammation in Alzheimer’s Disease

Cited by 18 publications

References 49 publications

In silico disrupting quorum sensing of porphyromonas gingivalis via essential oils and coumarin derivatives

In silico disrupting quorum sensing of porphyromonas gingivalis via essential oils and coumarin derivatives

Pyroptosis-Mediated Periodontal Disease

Impact of New Drugs for Therapeutic Intervention in Alzheimer’s Disease

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