IL-1β, IL-6, IL-10, and TNFα Single Nucleotide Polymorphisms in Human Influence the Susceptibility to Alzheimer’s Disease Pathology

Leko, Mirjana Babić; Perković, Matea Nikolac; Klepac, Nataša; Štrac, Dubravka Švob; Borovečki, Fran; Pivac, Nela; Hof, Patrick R.; Šimić, Goran

doi:10.3233/jad-200056

Cited by 44 publications

(30 citation statements)

References 130 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The TLR pathway is responsible for the maturation and release of IL-1β, one of the main pro-inflammatory cytokines involved in the pathophysiology of AD. In fact, IL-1β polymorphism is correlated with the age at AD onset in humans, whereas inhibition of its receptor recues cognitive impairment in animal models [88,89]. IL-1β is produced as a precursor, pro-IL-1β, and requires cleavage to become biologically active.…”

Section: Inflammatory Cascade In Alzheimer's Diseasementioning

confidence: 99%

Inflammatory Cascade in Alzheimer’s Disease Pathogenesis: A Review of Experimental Findings

Oliveira

Kucharska

Garcez

et al. 2021

Cells

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is the leading cause of dementia worldwide. Most AD patients develop the disease in late life, named late onset AD (LOAD). Currently, the most recognized explanation for AD pathology is the amyloid cascade hypothesis. It is assumed that amyloid beta (Aβ) aggregation and deposition are critical pathogenic processes in AD, leading to the formation of amyloid plaques, as well as neurofibrillary tangles, neuronal cell death, synaptic degeneration, and dementia. In LOAD, the causes of Aβ accumulation and neuronal loss are not completely clear. Importantly, the blood–brain barrier (BBB) disruption seems to present an essential role in the induction of neuroinflammation and consequent AD development. In addition, we propose that the systemic inflammation triggered by conditions like metabolic diseases or infections are causative factors of BBB disruption, coexistent inflammatory cascade and, ultimately, the neurodegeneration observed in AD. In this regard, the use of anti-inflammatory molecules could be an interesting strategy to treat, delay or even halt AD onset and progression. Herein, we review the inflammatory cascade and underlying mechanisms involved in AD pathogenesis and revise the anti-inflammatory effects of compounds as emerging therapeutic drugs against AD.

show abstract

Section: Inflammatory Cascade In Alzheimer's Diseasementioning

confidence: 99%

Inflammatory Cascade in Alzheimer’s Disease Pathogenesis: A Review of Experimental Findings

Oliveira

Kucharska

Garcez

et al. 2021

Cells

View full text Add to dashboard Cite

show abstract

“…Heatmaps showed a strong correlation between these hub genes and different immune factors. IL-10 single nucleotide polymorphisms were found to affect the susceptibility to AD pathology (Babić Leko et al, 2020 ; Yang et al, 2021 ). When stimulated by anti-inflammatory cytokines, macrophages are converted to the M2 phenotype.…”

Section: Discussionmentioning

confidence: 99%

Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease

Lai

Liu

et al. 2022

Front. Aging Neurosci.

View full text Add to dashboard Cite

Alzheimer's disease (AD), the most common neurodegenerative disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. Meanwhile, abnormalities in iron metabolism have been demonstrated in patients and mouse models with AD. Therefore, this study sought to find hub genes based on iron metabolism that can influence the diagnosis and treatment of AD. First, gene expression profiles were downloaded from the GEO database, including non-demented (ND) controls and AD samples. Fourteen iron metabolism-related gene sets were downloaded from the MSigDB database, yielding 520 iron metabolism-related genes. The final nine hub genes associated with iron metabolism and AD were obtained by differential analysis and WGCNA in brain tissue samples from GSE132903. GO analysis revealed that these genes were mainly involved in two major biological processes, autophagy and iron metabolism. Through stepwise regression and logistic regression analyses, we selected four of these genes to construct a diagnostic model of AD. The model was validated in blood samples from GSE63061 and GSE85426, and the AUC values showed that the model had a relatively good diagnostic performance. In addition, the immune cell infiltration of the samples and the correlation of different immune factors with these hub genes were further explored. The results suggested that these genes may also play an important role in immunity to AD. Finally, eight drugs targeting these nine hub genes were retrieved from the DrugBank database, some of which were shown to be useful for the treatment of AD or other concomitant conditions, such as insomnia and agitation. In conclusion, this model is expected to guide the diagnosis of patients with AD by detecting the expression of several genes in the blood. These hub genes may also assist in understanding the development and drug treatment of AD.

show abstract

“…TNF-α and IL-10 are important inflammatory factors leading to AS. TNF-α has been reported to promote the production of various inflammatory cytokines through T cells and has been identified as an important indicator of inflammation ( 35 ). Conversely, IL-10 has been reported to inhibit mononuclear macrophages from performing specific immune functions, such as the release of inflammatory mediators ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

Gentianella acuta mitigates cardiovascular damage and inflammation in diet‑induced hypercholesterolaemic rats

Huo

et al. 2021

Exp Ther Med

View full text Add to dashboard Cite

Gentianella acuta (G. acuta) has been widely used as a traditional medicine by Chinese Mongolian populations for the treatment of heart diseases and has also been tested in modern pharmacological experiments. However, the effects of G. acuta on cardiovascular damage and inflammation under conditions of hypercholesterolaemia remain unclear. The present study investigated the effects and mechanisms of the water extract of G. acuta on cardiovascular damage and inflammation caused by a high-cholesterol diet. Male Sprague-Dawley rats were fed a high-cholesterol diet for 4 weeks to establish the hypercholesterolaemia rat model, and they were administered physiological saline or 1.2 g/kg of G. acuta by gavage starting from the 15th day. After the last administration, the blood, heart and thoracic aorta samples were collected and examined. It was revealed that G. acuta treatment could ameliorate cardiomyocyte disorder and thoracic aortic vessel wall damage, reduce serum lipid levels and inflammatory factors and improve heart function. Compared with the Model group, the serum levels of triglycerides, total cholesterol, low-density lipoprotein and tumour necrosis factor-α were decreased, and the high-density lipoprotein and interleukin-10 levels were increased in the Model-G group. Moreover, in both the heart and thoracic aorta, G. acuta reduced the expression and phosphorylation of inhibitor of nuclear factor kappa-B kinase β (IKKβ), inhibitor of NF-κB-α (IκBα) and p-nuclear factor kappa-B (NF-κB). Therefore, G. acuta may exert an inhibitory effect on the IKK/IκB/NF-κB signalling pathway to protect the heart and thoracic aorta in hypercholesterolaemic rats.

show abstract

IL-1β, IL-6, IL-10, and TNFα Single Nucleotide Polymorphisms in Human Influence the Susceptibility to Alzheimer’s Disease Pathology

Cited by 44 publications

References 130 publications

Inflammatory Cascade in Alzheimer’s Disease Pathogenesis: A Review of Experimental Findings

Inflammatory Cascade in Alzheimer’s Disease Pathogenesis: A Review of Experimental Findings

Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease

Gentianella acuta mitigates cardiovascular damage and inflammation in diet‑induced hypercholesterolaemic rats

Contact Info

Product

Resources

About