Despite a clear correlation between the infiltration of periodontal pathogens in brain and cognitive decline Alzheimer's disease (AD), precise mechanism underlying bacteria crossing blood-brain barrier (BBB) remains unclear. The pathogen Porphyromonas gingivalis produces unique class cysteine proteases termed gingipains. Gingipains appear to be key virulence factors that exacerbate sporadic AD. We herein report gingipains are involved increasing permeability hCMEC/D3 cell monolayer, human...

Cathepsin B (CatB) is thought to be essential for the induction of Porphyromonas gingivalis lipopolysaccharide (Pg LPS)-induced Alzheimer’s disease-like pathologies in mice, including interleukin-1β (IL-1β) production and cognitive decline. However, little known about role CatB Pg virulence factor-induced IL-1β by microglia. We first subjected IL-1β-luciferase reporter BV-2 microglia inhibitors Toll-like receptors (TLRs), IκB kinase, NLRP3 inflammasome following stimulation with LPS outer...

Infection with Porphyromonas gingivalis (Pg), which is a major periodontal pathogen, causes large number of systemic diseases based on chronic inflammation such as diabetes, rheumatoid arthritis and Alzheimer’s disease. However, it remains unclear how Pg can augment local immune inflammatory responses, because its virulence factor lipopolysaccharide (LPS) have low biological activities. There strong association between depression elevated levels inflammation. Noradrenaline (NA) key...

Background Lipopolysaccharides from Porphyromonas gingivali s ( P.g LPS) are involved in the pathology of Alzheimer's disease (AD). However, effect LPS on synaptic defects remains unclear. Objective In this study, we tested our hypothesis that induces a low-amyloid-beta (Aβ)-concentration environment. Methods MG6 microglia or N2a neurons was treated with (0.1 μg/mL), soluble Aβ 42 μM) AL (combined and at 0.1 μM). Results cultured microglia, increased mRNA expression TNF-α, IL-1β IL-6 TNF-α...

Journal Article Phosphatidylserine recognition and induction of apoptotic cell clearance by Drosophila engulfment receptor Draper Get access Tran Thanh Tung, Tung 1Graduate School Natural Science Technology, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan; 2Department Pharmacology, Hanoi Medical No 1. Ton That Hanoi, Socialist Republic Vietnam; 3Graduate Sciences; 4School Pharmacy, Japan Search for other works this author on: Oxford Academic PubMed Google Scholar Kaz Nagaosa, Nagaosa...

To identify molecules that play roles in the clearance of apoptotic cells by Drosophila phagocytes, we examined a series monoclonal antibodies raised against larval hemocytes for effects on phagocytosis vitro. One antibody inhibited recognized terribly reduced optic lobes (Trol), core protein perlecan-type proteoglycan, and level embryos Trol-lacking fly line was lower than control line. The treatment hemocyte cell with recombinant Trol containing amino acid sequence RGD augmented...

Integrins exert a variety of cellular functions as heterodimers two transmembrane subunits named α and β. Integrin βν, β-subunit Drosophila integrin, is involved in the phagocytosis apoptotic cells bacteria. Here, we searched for an α-subunit that forms complex cooperates with βν. Examinations RNAi-treated animals suggested αPS3, but not any four other α-subunits, required effective embryos. The mutation αPS3-encoding scb, deficiency, insertion P-element, or alteration nucleotide sequences,...

Ingestion of Porphyromonas gingivalis, a periodontal pathogen, disrupts the intestinal barrier in mice. However, involvement outer membrane vesicles (OMVs) secreted from P. gingivalis destruction remains unclear. In this study, we tested hypothesis that OMVs carrying gingipains, major cysteine proteases produced by affects function. increased permeability Caco-2 cell monolayer, human epithelial line, accompanied degradation tight junction protein occludin. contrast, prepared mutant strains...

Much attention has been paid to the connection between periodontitis and Alzheimer's disease (AD). We previously showed that infection of P. gingivalis, one major periodontal pathogen causing periodontitis, induced migration inflammatory responses in murine microglia through gingipain-induced activation protease-activated receptor 2 (PAR2). In this study, we have attempted clarify effects secreted gingipains on cell human microglial line, cleavage sites PAR2 by subsequent signaling pathways....

Infection with Porphyromonas gingivalis (Pg), which is a major periodontal pathogen, causes large number of systemic diseases based on chronic inflammation such as diabetes and Alzheimer’s disease (AD). However, it not yet fully understood how Pg can augment local immune inflammatory responses during progression AD. There strong association between depression elevated levels inflammation. Noradrenaline (NA) key neurotransmitter that modulates microglial activation stress conditions. In this...

The phagocytic elimination of cells undergoing apoptosis is an evolutionarily conserved innate immune mechanism for eliminating unnecessary cells. Previous studies showed increase in the level engulfment receptors phagocytes after phagocytosis apoptotic cells, which leads to enhancement their activity. However, precise mechanisms underlying this phenomenon require further clarification. We found that pre-incubation a Drosophila phagocyte cell line with fragments enhanced subsequent...

The Drosophila Toll-1 receptor is involved in embryonic development, innate immunity, and tissue homeostasis. Currently, as a ligand for the receptor, only Spätzle (Spz) has been identified characterized. We previously reported that larva-derived extract contains activity which differs from Spz based on observation larval prepared spz mutants possessed full activity. Here, we demonstrate Spz5, member of family proteins, functions receptor. Processing Spz5 by Furin protease, known to be...

Pseudomonas entomophila is a highly pathogenic bacterium that infects insects. It also used as suitable model pathogen to analyze Drosophila’s innate immunity. P. entomophila’s virulence largely derived from Monalysin, β-barrel pore-forming toxin damages Drosophila tissues, inducing necrotic cell death. Here we report the first and efficient purification of endogenous Monalysin its characterization. successfully purified pro-form, trypsin treatment results in cleaved mature form kills lines...

Recently, the effects of antibacterial peptides are suggested to have therapeutic potential in Alzheimer’s disease. Furthermore, systemic treatment Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS) induced disease-like neuropathological changes middle-aged mice. Then, we examined whether human β-defensins (hBDs), antimicrobial produced by oral mucosa and salivary glands, can suppress Pg LPS-induced oxidative inflammatory responses microglia. hBD3 (1 μM) significantly suppressed...

Mutations in ATP13A2 cause Kufor-Rakeb Syndrome (KRS), a juvenile form of Parkinson’s Disease (PD). The gene product belongs to diverse family ion pumps and mediates polyamine influx from lysosomal lumen. While the biochemical structural studies highlight its unique mechanics, how PD pathology is linked function remains unclear. Here we report that localization overexpressed TOM20, mitochondrial outer-membrane protein, significantly altered upon expression partially merge with lysosome....

This work defines the ultrastructural responses of immortalized cells from inner medullary collecting duct (IMCD3 cells) to hypertonic challenges. The cultured were either acutely exposed medium (550 mOsm/kgH2O) for 24–72 h or gradually adapted 600 900 mOsm/kgH2O media with sodium chloride. After short (24 h) challenges, there was an expansion Golgi apparatus distinct expression γ subunit Na,K-ATPase. frequency active caspase-3-positive unchanged as also measured activity caspase-3....

Cathepsin B (CatB) is thought to be essential for the induction of Porphyromonas gingivalis lipopolysaccharide (Pg LPS)-induced Alzheimer’s disease- like pathologies in mice, including interleukin-1β (IL-1β) production and cognitive decline. However, little known about role CatB Pg virulence factor-induced IL-1β by microglia. We first subjected IL-1β-luciferase reporter BV-2 microglia inhibitors Toll-like receptors (TLRs), IκB kinase, NLRP3 inflammasome following stimulation with LPS outer...