BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relation...BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration,particularly the involvement of Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis.Experimental mouse models have been used to explore how P.gingivalis products contribute to neuroinflammatory and degenerative processes.However,a comprehensive synthesis of these findings is lacking.This systematic review evaluates the role of P.gingivalisderived factors in triggering Alzheimer's-like pathology,with an emphasis on bacterial products and host immune responses.We hypothesize that P.gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.AIM To link gingival P.gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.METHODS This systematic review followed the 2020 PRISMA guidelines.A comprehensive search was conducted in five databases(PubMed,Scopus,ScienceDirect,Sage,SpringerLink)for original studies between 2014 and 2024.Studies included mouse models to evaluate the effect of P.gingivalis or its products on Alzheimer's-like pathologies.Exclusion criteria were in vitro,human,or review studies.Twenty-three studies met the inclusion criteria.Bacterial components and activated host factors were extracted,categorized,and analyzed using narrative synthesis and descriptive statistics.RESULTS In 24 studies,lipopolysaccharides(54.84%)and gingipains(25.81%)were the most frequently reported P.gingivalis products.These factors activated toll-like receptors(TLR2/TLR4),microglia,and astrocytes,increasing levels of interleukin 1 beta,tumor necrosis factor-alpha,and other proinflammatory cytokines.The host response includedβ-amyloid accumulation,Tau hyperphosphorylation,and changes in blood-brain barrier permeability.Glial cells were the most frequently mentioned host factors(n=15),followed by proteins(n=13)and cytokines(n=11).These interactions promoted cognitive impairment,synaptic dysfunction,and neurodegeneration in mouse models,supporting a role for P.gingivalis in Alzheimer's-like pathology.CONCLUSION P.gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models,supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.展开更多
Alzheimer’s disease has proven to be largely intractable to treatment,despite years of research,and numerous trials of therapies that target the hallmarks of the disease-amyloid plaques and neurofibrillary tangles.Th...Alzheimer’s disease has proven to be largely intractable to treatment,despite years of research,and numerous trials of therapies that target the hallmarks of the disease-amyloid plaques and neurofibrillary tangles.The etiology of Alzheimer’s disease remains elusive.There is a growing body of evidence for an infectious trigger of Alzheimer’s disease,and,in particular,the focus has been on the oral pathogen Porphyromonas gingivalis(P.gingivalis).Reports of the expression of a misfolded form of p53 in non-neuronal cells(fibroblasts,peripheral blood mononuclear cells,and B cells)and serum,which appears several years before clinical symptoms manifest,may provide further support for the role of bacteria in general,and P.gingivalis in particular,in the initiation of the disease.This review presents a model of the pathway from initial oral infection with P.gingivalis to amyloid plaque formation and neuronal degeneration,via the steps of chronic periodontitis;secretion of the inflammagens lipopolysaccharide and gingipains into the bloodstream;induction of an inflammatory response in both peripheral cells and tissues;disruption of the blood-brain barrier,and entry into the central nervous system of the inflammagens and the P.gingivalis bacteria themselves.In this model,the misfolded p53(or“unfolded p53”;up53)is induced in non-neuronal cells and upregulated in serum as a result of oxidative stress due to lipopolysaccharide from P.gingivalis.up53 is therefore a potential biomarker for early diagnosis of the presence of a causative agent of Alzheimer’s disease.Fastidious dental hygiene and aggressive antibiotic treatment may prevent the patient progressing to clinical Alzheimer’s disease if serum up53 is detected at this pre-symptomatic stage.展开更多
BACKGROUND： Porphyromonas gingivalis is a periodontal pathogen, which is considered to be a keystone pathogen for periodontitis. A diverse conglomerate of P. gingivalis virulence factors including lipopolysaccharide,...BACKGROUND： Porphyromonas gingivalis is a periodontal pathogen, which is considered to be a keystone pathogen for periodontitis. A diverse conglomerate of P. gingivalis virulence factors including lipopolysaccharide, fimbriae, capsular polysaccharide, haemagglutinin and cysteine proteases （Arg-gingipains and Lys-gingipain） are considered to be involved in the pathogenesis ofperiodontitis. Leupeptin is a cysteine protease inhibitor which is specific for Arg gingipains. The present review focuses on action of leupeptin on Arg gingipains. METHOD： A search was carried out systematically from the start till September, 2016. The search was made in Medline database via PubMed. The keywords enlisted were ＂leupeptin＂; ＂gingipains＂; ＂periodontitis＂ using Boolean operator ＂and.＂ RESULTS： The result was selection of 58 articles which linked leupeptin to periodontitis and gingipains; pathogenesis of periodontitis, pathogenicity of gingipains and role of leupeptin. CONCLUSION： It was concluded that leupeptin inhibits and attenuates a number of destructive activities of Arg gingipains including inhibition ofplatelet aggregation; inhibit degradation of LL-37, which is an antimicrobial peptide; blocking inhibition ofmonocyte chemoattractant protein; restoring level ofinterleukin-2; inhibiting degradation of collagen type I and IV to name a few.展开更多
文摘BACKGROUND Alzheimer's disease is a neurodegenerative dementia characterized by accumulation ofβ-amyloid plaques,tau hyperphosphorylation,and neuroinflammation.Recent research has highlighted a potential relationship between chronic oral infections and neurodegeneration,particularly the involvement of Porphyromonas gingivalis(P.gingivalis),a key pathogen in periodontitis.Experimental mouse models have been used to explore how P.gingivalis products contribute to neuroinflammatory and degenerative processes.However,a comprehensive synthesis of these findings is lacking.This systematic review evaluates the role of P.gingivalisderived factors in triggering Alzheimer's-like pathology,with an emphasis on bacterial products and host immune responses.We hypothesize that P.gingivalis products exacerbate neuroinflammation and pathology in mouse models of Alzheimer's disease.AIM To link gingival P.gingivalis bacteria-associated products with the onset and progression of Alzheimer's disease-like pathology in mouse models.METHODS This systematic review followed the 2020 PRISMA guidelines.A comprehensive search was conducted in five databases(PubMed,Scopus,ScienceDirect,Sage,SpringerLink)for original studies between 2014 and 2024.Studies included mouse models to evaluate the effect of P.gingivalis or its products on Alzheimer's-like pathologies.Exclusion criteria were in vitro,human,or review studies.Twenty-three studies met the inclusion criteria.Bacterial components and activated host factors were extracted,categorized,and analyzed using narrative synthesis and descriptive statistics.RESULTS In 24 studies,lipopolysaccharides(54.84%)and gingipains(25.81%)were the most frequently reported P.gingivalis products.These factors activated toll-like receptors(TLR2/TLR4),microglia,and astrocytes,increasing levels of interleukin 1 beta,tumor necrosis factor-alpha,and other proinflammatory cytokines.The host response includedβ-amyloid accumulation,Tau hyperphosphorylation,and changes in blood-brain barrier permeability.Glial cells were the most frequently mentioned host factors(n=15),followed by proteins(n=13)and cytokines(n=11).These interactions promoted cognitive impairment,synaptic dysfunction,and neurodegeneration in mouse models,supporting a role for P.gingivalis in Alzheimer's-like pathology.CONCLUSION P.gingivalis products induce neuroinflammatory responses and Alzheimer's-like pathology in mouse models,supporting their role as contributors to neurodegeneration and potential targets for preventive strategies.
文摘Alzheimer’s disease has proven to be largely intractable to treatment,despite years of research,and numerous trials of therapies that target the hallmarks of the disease-amyloid plaques and neurofibrillary tangles.The etiology of Alzheimer’s disease remains elusive.There is a growing body of evidence for an infectious trigger of Alzheimer’s disease,and,in particular,the focus has been on the oral pathogen Porphyromonas gingivalis(P.gingivalis).Reports of the expression of a misfolded form of p53 in non-neuronal cells(fibroblasts,peripheral blood mononuclear cells,and B cells)and serum,which appears several years before clinical symptoms manifest,may provide further support for the role of bacteria in general,and P.gingivalis in particular,in the initiation of the disease.This review presents a model of the pathway from initial oral infection with P.gingivalis to amyloid plaque formation and neuronal degeneration,via the steps of chronic periodontitis;secretion of the inflammagens lipopolysaccharide and gingipains into the bloodstream;induction of an inflammatory response in both peripheral cells and tissues;disruption of the blood-brain barrier,and entry into the central nervous system of the inflammagens and the P.gingivalis bacteria themselves.In this model,the misfolded p53(or“unfolded p53”;up53)is induced in non-neuronal cells and upregulated in serum as a result of oxidative stress due to lipopolysaccharide from P.gingivalis.up53 is therefore a potential biomarker for early diagnosis of the presence of a causative agent of Alzheimer’s disease.Fastidious dental hygiene and aggressive antibiotic treatment may prevent the patient progressing to clinical Alzheimer’s disease if serum up53 is detected at this pre-symptomatic stage.
文摘BACKGROUND： Porphyromonas gingivalis is a periodontal pathogen, which is considered to be a keystone pathogen for periodontitis. A diverse conglomerate of P. gingivalis virulence factors including lipopolysaccharide, fimbriae, capsular polysaccharide, haemagglutinin and cysteine proteases （Arg-gingipains and Lys-gingipain） are considered to be involved in the pathogenesis ofperiodontitis. Leupeptin is a cysteine protease inhibitor which is specific for Arg gingipains. The present review focuses on action of leupeptin on Arg gingipains. METHOD： A search was carried out systematically from the start till September, 2016. The search was made in Medline database via PubMed. The keywords enlisted were ＂leupeptin＂; ＂gingipains＂; ＂periodontitis＂ using Boolean operator ＂and.＂ RESULTS： The result was selection of 58 articles which linked leupeptin to periodontitis and gingipains; pathogenesis of periodontitis, pathogenicity of gingipains and role of leupeptin. CONCLUSION： It was concluded that leupeptin inhibits and attenuates a number of destructive activities of Arg gingipains including inhibition ofplatelet aggregation; inhibit degradation of LL-37, which is an antimicrobial peptide; blocking inhibition ofmonocyte chemoattractant protein; restoring level ofinterleukin-2; inhibiting degradation of collagen type I and IV to name a few.
