Cellular and molecular influencers of neuroinflammation in Alzheimer's disease: Recent concepts &amp; roles

Ghosh, Powsali; Singh, Ravi Bhushan; Ganeshpurkar, Ankit; Pokle, Ankit Vyankatrao; Singh, Sushil Kumar; Kumar, Ashok

doi:10.1016/j.neuint.2021.105212

Cited by 30 publications

(17 citation statements)

References 252 publications

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“…Previous data from our group showed that HPU can modulate signaling pathways involving lipoxygenase-derived eicosanoids and alter intracellular calcium levels in rabbit platelets, human neutrophils and human endothelial cells [ 28 , 34 , 78 ]. Eicosanoids are known to be involved in neuroinflammation [ 79 , 80 ], a condition that also exists in AD [ 81 , 82 ].…”

Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Urease: Potential Contributions to Alzheimer’s Disease

Uberti

Callai-Silva

Grahl

et al. 2022

IJMS

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Alzheimer’s disease (AD) causes dementia and memory loss in the elderly. Deposits of beta-amyloid peptide and hyperphosphorylated tau protein are present in a brain with AD. A filtrate of Helicobacter pylori’s culture was previously found to induce hyperphosphorylation of tau in vivo, suggesting that bacterial exotoxins could permeate the blood–brain barrier and directly induce tau’s phosphorylation. H. pylori, which infects ~60% of the world population and causes gastritis and gastric cancer, produces a pro-inflammatory urease (HPU). Here, the neurotoxic potential of HPU was investigated in cultured cells and in rats. SH-SY5Y neuroblastoma cells exposed to HPU (50–300 nM) produced reactive oxygen species (ROS) and had an increased [Ca2+]i. HPU-treated BV-2 microglial cells produced ROS, cytokines IL-1β and TNF-α, and showed reduced viability. Rats received daily i.p., HPU (5 µg) for 7 days. Hyperphosphorylation of tau at Ser199, Thr205 and Ser396 sites, with no alterations in total tau or GSK-3β levels, and overexpression of Iba1, a marker of microglial activation, were seen in hippocampal homogenates. HPU was not detected in the brain homogenates. Behavioral tests were performed to assess cognitive impairments. Our findings support previous data suggesting an association between infection by H. pylori and tauopathies such as AD, possibly mediated by its urease.

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Section: Discussionmentioning

confidence: 99%

Helicobacter pylori Urease: Potential Contributions to Alzheimer’s Disease

Uberti

Callai-Silva

Grahl

et al. 2022

IJMS

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“…5 It is the predominant type of dementia across the world, accounting for approximately 70% of all cases, 6 and is one of the leading causes of death globally. 7 Recent studies have reported AD development to be a comorbidity with other pathologies, including type 2 diabetes, obesity, and cardiovas-cular disease. 8 There is also an increased risk of metabolic syndrome, which has been observed in both human population-based surveys and AD-related mice models.…”

Section: Introductionmentioning

confidence: 99%

Helicobacter pylori and Alzheimer’s Disease-Related Metabolic Dysfunction: Activation of TLR4/Myd88 Inflammation Pathway from p53 Perspective and a Case Study of Low-Dose Radiation Intervention

Zhao

Shen

Zhou

et al. 2022

ACS Chem. Neurosci.

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Gut dysbiosis is observed in Alzheimer's disease (AD) and is frequently associated with AD-induced metabolic dysfunction. However, the extent and specific underlying molecular mechanisms triggered by alterations of gut microbiota composition and function mediating ADinduced metabolic dysfunction in AD remain incompletely uncovered. Here, we indicate that Helicobacter pylori (H. pylori) is abundant in AD patients with relative metabolic dysfunction. Fecal microbiota transplantation from the AD patients promoted metabolic dysfunction in mice and increased gut permeability. H. pylori increased gut permeability through activation of the TLR4/Myd88 inflammation pathway in a p53-dependent manner, leading to metabolic dysfunction. Moreover, p53 deficiency reduced bile acid concentration, leading to an increased abundance of H. pylori colonization. Overall, these data identify H. pylori as a key promoter of ADinduced metabolic dysfunction.

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“…This abnormal clearance of neuro proteins leads to synaptic dysfunction, which eventually results in the occurrence and progression of AD. 37 In this process, the activation of microglia is the key element of neuroinflammation. 34 Recently, it has been shown that microglial activation and tau accumulation appear simultaneously and colocalize in the living human brain, which crucially proved that the activation of microglia is not just a result of disease progression, but rather a key upstream mechanism for AD's progression.…”

Section: The Role Of Microglia Cellsmentioning

confidence: 99%

“…Chronic inflammation dysregulates the clearance of misfolded tau proteins through cellular and molecular influence. This abnormal clearance of neuro proteins leads to synaptic dysfunction, which eventually results in the occurrence and progression of AD 37 . In this process, the activation of microglia is the key element of neuroinflammation 34 .…”

Section: Introductionmentioning

confidence: 99%

Periodontal microorganisms and Alzheimer disease – A causative relationship?

Jungbauer

Stähli

Zhu

et al. 2022

Periodontology 2000

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In the initiation or exacerbation of Alzheimer disease, the dissemination of oral microorganisms into the brain tissue or the low‐level systemic inflammation have been speculated to play a role. However, the impact of oral microorganisms, such as Porphyromonas gingivalis, on the pathogenesis of Alzheimer disease and the potential causative relationship is still unclear. The present review has critically reviewed the literature by examining the following aspects: (a) the oral microbiome and the immune response in the elderly population, (b) human studies on the association between periodontal and gut microorganisms and Alzheimer disease, (c) animal and in vitro studies on microorganisms and Alzheimer disease, and (d) preventive and therapeutic approaches. Factors contributing to microbial dysbiosis seem to be aging, local inflammation, systemic diseases, wearing of dentures, living in nursing homes and no access to adequate oral hygiene measures. Porphyromonas gingivalis was detectable in post‐mortem brain samples. Microbiome analyses of saliva samples or oral biofilms showed a decreased microbial diversity and a different composition in Alzheimer disease compared to cognitively healthy subjects. Many in‐vitro and animal studies underline the potential of P gingivalis to induce Alzheimer disease‐related alterations. In animal models, recurring applications of P gingivalis or its components increased pro‐inflammatory mediators and β‐amyloid in the brain and deteriorated the animals' cognitive performance. Since periodontitis is the result of a disturbed microbial homoeostasis, an effect of periodontal therapy on the oral microbiome and host response related to cognitive parameters may be suggested and should be elucidated in further clinical trials.

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Cellular and molecular influencers of neuroinflammation in Alzheimer's disease: Recent concepts & roles

Cited by 30 publications

References 252 publications

Helicobacter pylori Urease: Potential Contributions to Alzheimer’s Disease

Helicobacter pylori Urease: Potential Contributions to Alzheimer’s Disease

Helicobacter pylori and Alzheimer’s Disease-Related Metabolic Dysfunction: Activation of TLR4/Myd88 Inflammation Pathway from p53 Perspective and a Case Study of Low-Dose Radiation Intervention

Periodontal microorganisms and Alzheimer disease – A causative relationship?

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