Zebrafish Study Provides Evidence for Porphyromonas gingivalis Outer Membrane Vesicles Eliciting Alzheimer's Disease-Like Pathologies
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ABSTRACT:
ORGANISM(S): Danio Rerio
SUBMITTER: 
Jianbin Guo
PROVIDER: PXD067862 | iProX | Fri Aug 29 00:00:00 BST 2025
REPOSITORIES: iProX
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Project description:The outer membrane vesicles (OMVs) produced by Porphyromonas gingivalis (P. gingivalis) contain a variety of bioactive molecules that may be involved in the progression of periodontitis. However, the participation of P. gingivalis OMVs in the development of periodontitis has not been elucidated. Here we isolated P. gingivalis OMVs and confirmed their participation in periodontitis both in vivo and in vitro. Microcomputed Tomography (micro-CT) and histological analysis showed that under the stimulation of P. gingivalis OMVs, the alveolar bone of rats was significantly resorbed in vivo. We found that P. gingivalis OMVs were taken up by hPDLCs (human Periodontal Ligament Cells, hPDLCs) in vitro, then subsequently resulting in apoptosis and inflammatory cytokines releasing which was accomplished by the microRNA-size small RNAs (msRNAs) sRNA45033 in the P. gingivalis OMVs. Through bioinformatics analysis and screening of target genes, Chromobox 5 (CBX5) was identified as the downstream target of screened-out small RNA s45033. Using dual-luciferase reporter assay, overexpression, and knockdown methods, s45033 was confirmed to target CBX5 to regulate hPDLCs apoptosis. In addition, Cleavage Under Targets and Tagmentation (Cut&Tag) analysis confirmed the mechanism that CBX5 regulates apoptosis through the methylation of p53 DNA. Collectively, these findings indicate that the role of P. gingivalis OMVs is immunologically relevant and related to bacterial virulence in the development of periodontitis.
2022-11-30 | GSE218606 | GEO
Project description:Porphyromonas gingivalis is a key pathogen in the development of chronic periodontitis and has recently been linked to the development of rheumatoid arthritis and Alzheimer’s disease. In this project the outer membrane vesicles (OMV) from Pg have been analyzed using a two-dimensional HFBA-based separation system combined with LC-MS. Three strains from P. gingivalis was analyzed in order to elucidate their citrullinome: wild-type (WT), a mutant with the active site cysteine mutated to alanine (C351A), as well as a knock-out mutant of peptidyl arginine deiminase (ΔPPAD). For optimal and positive identification and validation of citrullinated peptides and proteins, high resolution mass spectrometers and strict MS criteria were utilized. This may have compromised the total number of identified citrullination, but increased the confidence of the validation. A new 2D separation system proved to increase the strength of validation, and along with the use of an in-house build program, Citrullia, we establish a fast and easy semi-automatic (manual) validation of citrullinated peptides. For WT we identified 78 citrullinated proteins having a total of 161 citrullination sites. For C351A a single citrullination site was found and no citrullinations was found for ΔPPAD.
2019-11-22 | PXD015701 | Pride
Project description:Periodontitis patients exhibit significant upregulation of the cholinergic signaling pathway in gingival epithelial cells, accompanied by elevated acetylcholine (ACh) levels in saliva. However, the role of ACh in the pathogenesis of periodontitis remains unclear. P. gingivalis, a keystone pathogen in periodontitis, triggers host inflammatory responses and compromises the epithelial barrier function. As the first line of defense against pathogens, the reparative capacity of the oral epithelium critically influences the progression of periodontitis. This study investigates whether ACh modulates P. gingivalis-induced inflammatory responses and epithelial repair in human oral keratinocytes (HOKs), aiming to elucidate the mechanistic role of cholinergic signaling in periodontitis.
2025-05-21 | GSE297378 | GEO
Project description:Periodontitis and infections with periodontal bacteria have been highlighted as risk factors for dementia. In recent years attention has been drawn to the role of microglia cells in neurodegenerative diseases. However, there is limited knowledge of the influence of periodontal bacteria on microglia cells. The aim of the present study was to investigate the interactions between the periodontal bacteria P. gingivalis and microglia cells, and to unravel if these interactions could contribute to Alzheimer’s pathology. Periodontitis and infections with periodontal bacteria have been highlighted as risk factors for dementia. In recent years attention has been drawn to the role of microglia cells in neurodegenerative diseases. However, there is limited knowledge of the influence of periodontal bacteria on microglia cells. The aim of the present study was to investigate the interactions between the periodontal bacteria P. gingivalis and microglia cells, and to unravel if these interactions could contribute to Alzheimer’s pathology. We found, through microarray analysis, that stimulation of microglia cells with P. gingivalis resulted in upregulation of several Alzheimer´s disease associated genes, including NOX4. We also showed that P. gingivalis LPS mediated ROS production and IL-6 and IL-8 induction via NOX4 in microglia. The viability of neurons was shown to be reduced by conditioned media from microglia cells stimulated with P. gingivalis LPS, and that the reduction was NOX4 dependent. The levels of total and phosphorylated Tau in neurons were increased by conditioned media from microglia cells stimulated with P. gingivalis or LPS. This increase was NOX4 dependent. In summary our findings give us a potential mechanistic explanation of how the periodontal pathogen P. gingivalis could trigger or exacerbate AD pathogenesis.
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Project description:Growing data suggest companion dogs may be a promising model of human brain aging and Alzheimer’s disease (AD). However, while pathology is similar in AD and canine cognitive dysfunction (CCD), the transcriptomic similarities between these two conditions have not been thoroughly evaluated. Two emerging transcriptome-related mechanisms of brain aging and AD involve transposable elements (TEs) and microRNAs (miRNAs), which have the potential to be carried systemically and between cells by extracellular vesicles (EVs). To determine if evidence of these AD-related transcriptomic events might be present in CCD, we generated total transcriptome (RNA-seq) data on cortex tissue and plasma EVs from young, old, and old CCD dogs. We show that: 1) global transcriptome changes with CCD indicate reduced neuronal health; 2) TE transcripts increase with CCD in both the brain and plasma EVs; 3) brain- and disease-relevant miRNAs are present in the same EVs, and some of these miRNAs correlate with indices of cognitive function/CCD. Collectively, our data suggest that transcriptomic changes in the dog, including those related to novel RNA mechanisms of brain aging and disease, are similar to those observed in humans.
2025-08-04 | GSE304125 | GEO
Project description:Porphyromonas gingivalis is a gram-negative bacterium that causes destructive chronic periodontitis. In addition, this bacterium is also involved in the development of cardiovascular disease. The aim of this study was to investigate the effects of P. gingivalis infection on gene and protein expression in human aortic smooth muscle cells (AoSMCs) and its relation to cellular function.
2013-11-17 | E-MTAB-1922 | biostudies-arrayexpress
Project description:INTRODUCTION: Omics studies have revealed that various brain cell types undergo profound molecular changes in Alzheimer’s disease (AD) but the spatial relationships with plaques and tangles and APOE-linked differences remain unclear. METHODS: We performed laser capture microdissection of Ab plaques, the 50mm halo around them, tangles with the 50mm halo around them, and areas distant (>50mm) from plaques and tangles in the temporal cortex of AD and control donors, followed by RNA-sequencing. RESULTS: Ab plaques exhibited upregulated microglial (neuroinflammation) and downregulated neuronal (neurotransmission/energy metabolism) genes, whereas tangles had mostly downregulated neuronal genes. Ab plaques had more differentially expressed genes than tangles. We identified a gradient Ab plaque>peri-plaque>tangle>distant for these changes. AD APOEe4 homozygotes had greater changes than APOEe3 across locations, especially within Ab plaques. DISCUSSION: Transcriptomic changes in AD consist primarily of neuroinflammation and neuronal dysfunction, are spatially associated mainly with Ab plaques, and are exacerbated by the APOEe4 allele.
2024-02-14 | GSE226901 | GEO
Project description:Alzheimer’s disease (AD) is characterized by neuroinflammation, accumulation of amyloid-β (Aβ) plaques and neuronal degeneration in the brain. The APOE4 variant of apolipoprotein E (apoE) is the most prevalent genetic risk allele associated with late-onset AD. ApoE interacts with complement regulator factor H (FH) but the role of this interaction in AD pathogenesis is unknown.
2023-05-03 | GSE193513 | GEO
Project description:Amyloid protein deposit, like Aβ plaques, is a pathological hallmark of Alzheimer’s disease (AD). While plenty of amyloid imaging reagents available for diagnosis, their composition associated with disease etiology is challenging to analyze in intact tissue sample. Herein, we report an amyloid-targeting probe to photocatalyze in-situ labeling and profiling of Aβ plaques in AD brain tissue via single electron transfer (SET) mechanism. First, we render this amyloid probe with photocatalytic labeling function by fragment fusion of classical scaffolds of fluorescent amyloid sensors. Second, we demonstrate its labeling selectivity to amyloid proteins over monomer counterparts. Mechanistically, we show spatially resolved labeling is driven by the short-lived SET photocatalytic process. Finally, we use this probe to capture and profile the composition of amyloid plagues in Alzheimer’s disease brain tissue. Surpassing other AD proteomics datasets, our work spatially resolves pathogenic Aβ and typical AD biomarkers as top-ranked hits. Together, the short-lived SET-driven photocatalysis spatially restrains protein labeling to occur in ultra-proximity to amyloids, allowing for microscope-free amyloid tissue microdissection at molecular level.
2025-01-13 | PXD059374 | Pride
Project description:Porphyromonas gingivalis outer membrane vesicles promote apoptosis via msRNA-regulated DNA methylation in periodontitis
| PRJNA904498 | ENA