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Potential AD-associated mechanism of IL1, IL6 and TNF alpha pro-inflammatory factors: Injury in CNS and Abeta aggregates can increase the microglial activation and the production of pro-inflammatory molecules. These cytokines bind to their receptors, resulting in the activation of signaling cascade inside the cell, which result changes in gene expression. This cascade can induce the elevated expression and overproduction of pro-inflammatory factors, resulting in neuro-inflammation and neuronal loss. IL6 and IL1 might also be involved in abnormal phosphorylation of Tau protein, which can also contribute to cell death 31,50
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Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia, several genetic, non-genetic, and environmental factors could be involved in disease progression. Association was suggested between inflammation and AD progression. Since neuroinflammation can be involved in neurodegeneration, studies suggested that several inflammatory...
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... can affect through different mechanisms, associated with AD, such as it might change the synaptic plasticity. In addition, it might induce the Tau phosphorylation and NFT formation (Figure 2.). ...
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... the frontal and occipital cortex of AD brain, the expression of IL6R was increased, but decreased levels were found in temporal cortex and cerebellum 17 . Quintanilla et al. (2004) suggested that stimulation of IL6 pathway could increase the protein kinases, leading to enhanced Tau phosphorylation (Figure 2.) and elevated AD-type epitope expression on Tau protein 18 . Soluble IL6 receptors (IL6sR) could bind to IL6 in solution, and IL6-IL6R complex might be associated with pro-inflammatory cascade mechanisms, leading to neurodegeneration19 (Figure 2.). ...
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... et al. (2004) suggested that stimulation of IL6 pathway could increase the protein kinases, leading to enhanced Tau phosphorylation (Figure 2.) and elevated AD-type epitope expression on Tau protein 18 . Soluble IL6 receptors (IL6sR) could bind to IL6 in solution, and IL6-IL6R complex might be associated with pro-inflammatory cascade mechanisms, leading to neurodegeneration19 (Figure 2.). ...
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... of TNF, was induced by Abeta but the cytoprotective effect of TNF was also validated. Combination of TNF, IL1 and IL6 might be a promising biomarker of AD, since all of them can be associated with A-induced microglial activation (Figure 2.) 44 . TNF could intract with high affinity receptors (TNFRI and II), which are located on several cell types. ...
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... Figure 2 is not fully described either in text or in figure legend. Moreover, Figure 2 itself does not show strong relevance to AD (A beta is only AD related marker in Fig. 2). ...
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... Figure 2 is not fully described either in text or in figure legend. Moreover, Figure 2 itself does not show strong relevance to AD (A beta is only AD related marker in Fig. 2). In Figure 2, some items such as TNFalpha trimer, TNFR, gp130, Tau phosphorylation, and etc are not described at all in the figure legend and poorly mentioned in the text. ...
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... Figure 2 is not fully described either in text or in figure legend. Moreover, Figure 2 itself does not show strong relevance to AD (A beta is only AD related marker in Fig. 2). In Figure 2, some items such as TNFalpha trimer, TNFR, gp130, Tau phosphorylation, and etc are not described at all in the figure legend and poorly mentioned in the text. NFkappaB is mentioned in Fig 2 legend, but ...
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... Figure 2 itself does not show strong relevance to AD (A beta is only AD related marker in Fig. 2). In Figure 2, some items such as TNFalpha trimer, TNFR, gp130, Tau phosphorylation, and etc are not described at all in the figure legend and poorly mentioned in the text. NFkappaB is mentioned in Fig 2 legend, but ...
Citations
... Rheumatoid arthritis, associated vasculitis, Alzheimer's disease, inflammatory bowel disease, severe acute respiratory syndrome [84][85][86][87][88] High-mobility group box 1 (HMGB1) Atherosclerosis, COVID-19, influenza [89][90][91] Enzymatic anti-oxidants superoxide dismutase (SOD), glutathione peroxidase (GPx), NADPH oxidase2 (NOX2), inducible nitric oxide synthase (iNOS), cyclooxigenase, (COX-2) ...
Chronic inflammatory diseases, such as cancer, diabetes mellitus, stroke, ischemic heart diseases, neurodegenerative conditions, and COVID-19 have had a high number of deaths worldwide in recent years. The accurate detection of the biomarkers for chronic inflammatory diseases can significantly improve diagnosis, as well as therapy and clinical care in patients. Graphene derivative materials (GDMs), such as pristine graphene (G), graphene oxide (GO), and reduced graphene oxide (rGO), have shown tremendous benefits for biosensing and in the development of novel biosensor devices. GDMs exhibit excellent chemical, electrical and mechanical properties, good biocompatibility, and the facility of surface modification for biomolecular recognition, opening new opportunities for simple, accurate, and sensitive detection of biomarkers. This review shows the recent advances, properties, and potentialities of GDMs for developing robust biosensors. We show the main electrochemical and optical-sensing methods based on GDMs, as well as their design and manufacture in order to integrate them into robust, wearable, remote, and smart biosensors devices. We also describe the current application of such methods and technologies for the biosensing of chronic disease biomarkers. We also describe the current application of such methods and technologies for the biosensing of chronic disease biomarkers with improved sensitivity, reaching limits of detection from the nano to atto range concentration.
... Reducing inflammatory markers can not only mitigate the uncomfortable symptoms of RA but also benefit synaptic and neuronal integrity, which in turn lessens the individual's susceptibility to cognitive impairment disorders. Recent evidence demonstrated that the above-mentioned inflammatory markers might play pivotal roles in the development or pathology of neurodegenerative diseases (26,27). Second, a previous study also found the activation of intracellular signaling pathways, especially brain-derived neurotrophic factor (BDNF)-tyrosine receptor kinase B (TrkB), may account for the positive link between RS utilization and lower risk of neurological disorders (28). ...
Objectives: Rheumatoid arthritis (RA) was found to trigger the higher risk of dementia. Limited information, however, is available on whether the use of rehabilitation services (RS), an integral part of healthcare programs, can lessen dementia risk for RA subjects. The aim of this study was to determine the relationship of RS use to the development of dementia in RA patients.
Methods: We identified 2,927 newly diagnosed patients with RA, 20–70 years of age between 1998 and 2007, from a national health insurance database. 965 patients from this sample received RS, and 1,962 patients were designated as a control group (non-RS users). Patients were followed to the end of 2012 to identify dementia incident as the end point. Cox proportional hazards regression was performed to calculate the hazard ratio (HR) of dementia risk associated with the use of RS.
Results: During the study period, 388 patients with RS and 1,224 controls developed dementia, representing incidence rate of 75.46 and 115.42 per 1,000 person-years, respectively. After adjusting for potential confounders, RS was found to significantly reduce dementia risk, with the adjusted HR of 0.60 (95% confidence interval [CI] = 0.53–0.67). Those who used the high intensity of RS (≧15 courses) had the greatest benefit.
Conclusions: Integrating RS into the conventional treatment may reduce the sequent risk of dementia for RA patients.
... 20 Recent studies have demonstrated that inflammatory markers, such as interlukin-1β, IL-6, and tumor necrosis factor-α (TNF-α), play key roles in the pathogenesis of neurodegenerative disorders. 21,22 Second, evidence also indicates that the link between acupuncture use and lower risk of neurological disorders occurs via the activation of intracellular signaling pathways, such as BDNF/TrkB and phosphatidylinositol 3-kinase (PI3K)/Akt. 13,23 By upregulating the BDNF-TrkB pathway, it could rescue neuronal cells from neurodegeneration due to injuries in the central nervous system and further prevent oxidative damage in many cultivated neurons. ...
... It is well known that estrogen can suppress production of inflammatory cytokines such as IL-1, IL-6, and TNF-α in the spinal cord, 27 all of which play decisive roles in the generation of neurodegenerative disorders. 21,22 The preexisting biochemical benefits provided by estrogen to younger women may insidiously enhance the therapeutic influence of acupuncture against the predisposition of developing dementia. Findings from the current study have important clinical and research implications. ...
Objective:
We conducted a longitudinal cohort study comparing the effect of acupuncture on the risk of dementia in Taiwanese individuals with traumatic brain injury (TBI).
Design and participants:
A national health insurance database was used to identify 15 440 newly diagnosed TBI patients 20 to 70 years old between 1998 and 2007. Of the identified patients, 6308 received acupuncture following the onset of TBI (acupuncture users) and 9132 patients did not receive acupuncture (nonacupuncture users).
Measures:
All enrollees were followed until the end of 2012 to record incident cases of dementia. A Cox proportional hazards regression model was used to compute adjusted hazard ratios for the relationship of acupuncture use with dementia.
Results:
During the follow-up period, 249 acupuncture users and 810 nonacupuncture users developed dementia, corresponding to incidence rates of 6.11 and 9.64 per 1000 person-years, respectively. Use of acupuncture was significantly associated with a lower risk of dementia. Those who received more than 5 sessions of acupuncture benefited most from it.
Conclusions:
Adding acupuncture to the clinical management of patients with TBI may benefit these patients by decreasing their risk of developing dementia.
... Various novel blood-and CSF-based biomarkers for AD have been proposed in recent years. These include (1) neuroinflammatory markers such as reactive oxygen species (ROS), cytokines, chemokines, astrocytes, and activated microglia; (2) proinflammatory molecules such as interleukins (ILs), interferons (IFNs), and tumour necrosis factors (TNFs); (3) autoantibodies; (4) trace elements such as copper, zinc, iron; (5) fatty acids, sphingolipids, ceramides; (6) micro-RNAs; (7) circulating nanocomponents; and others [26][27][28][29][30][31]. Alternatively, non-invasive neuroimaging techniques such as computerized tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) offer structural and functional information about the brain, which may be able to support a diagnosis of dementia, but only in the later stages when brain shrinkage is evident. ...
Cases of Alzheimer’s disease (AD) are rising exponentially due to increasing global life expectancy. There are approximately 50 million sufferers worldwide, with prevalence rising most rapidly in low-income countries such as Africa and Asia. There is currently no definite diagnosis of AD until after death, thus an early biomarker for AD is urgently required in order to administer timelier and more effective interventions. Olfactory dysfunction (problems with the sense of smell) is one of the earliest, preclinical symptoms observed in AD. Olfaction is a promising early biomarker for use worldwide as it is easy, cheap to measure, and not reliant on specialist clinicians or laboratory analysis. We carried out a meta-analysis to determine the credibility of olfaction in diagnosing AD in the preclinical stages, by comparing olfaction in healthy controls against AD patients and patients with mild cognitive impairment (MCI). Data from 10 articles were subjected to two comparative meta-analyses. In the case of AD, the results illustrated that the overall magnitude of effect size was more apparent, d = −1.63, 95% CI [−1.95, −1.31], in comparison to that of MCI, d = −0.81, 95% CI [−1.08, −0.55]. This shows that olfaction worsens progressively as patients progress from MCI to AD, highlighting the potential for olfactory dysfunction to identify AD in the preclinical stages prior to MCI.
... Moreover, resveratrol, a natural polyphenol reported to have anti-inflammatory effects, is able to up-regulate both IL-10 gene expression and IL-10 levels, which could explain its neuroprotective properties 32 . Bagyinszky et al. 22 disclosed that IL-10 treatment could be a potential therapy for AD since this cytokine could act on amyloid reduction by inducing the production of anti-inflammatory molecules, and inhibition of pro-inflammatory cytokines, probably by down-regulating their expression. ...
Alzheimer’s disease (AD) is the most common form of dementia. In the last 15 years, a new theory has proposed the autoimmune mechanism as a trigger for AD. Studies on the association between AD and inflammatory biomarkers have yielded controversial results. Interleukin-10 (IL-10), an anti-inflammatory mediator, has been pointed out as one of the main cytokines associated with the occurrence of AD. Moreover, treatment that increases IL-10 levels could be a potential therapy for AD, since this cytokine acts on amyloid and pro-inflammatory molecule reduction. Based on the current literature, this study reviews evidence regarding the role of IL-10 polymorphisms in the context of AD, which has been shown to be of paramount importance for attenuating neuroinflammation, cognitive dysfunction and neurodegeneration.
... It plays a role in several disorders, including rheumatoid arthritis, type-1 diabetes, and chronic heart failure [44]. Mutations in IL-1β were described as potential genetic risk factors for dementia [45]. IL-1β activity was increased in the AD brain [46]. ...
Alzheimer's disease (AD) is a complex disorder and the most common form of neurodegenerative dementia. Several genetic, environmental, and physiological factors, including inflammations and metabolic influences, are involved in the progression of AD. Inflammations are composed of complicated networks of many chemokines and cytokines with diverse cells. Inflammatory molecules are needed for the protection against pathogens, and maintaining their balances is important for normal physiological function. Recent studies demonstrated that inflammation may be involved in neurodegenerative dementia. Cellular immune components, such as microglia or astrocytes, mediate the release of inflammatory molecules, including tumor necrosis factor, growth factors, adhesion molecules, or chemokines. Over- and underexpression of pro- and anti-inflammatory molecules, respectively, may result in neuroinflammation and thus disease initiation and progression. In addition, levels of several inflammatory factors were reported to be altered in the brain or bodily fluids of patients with AD, reflecting their neuropathological changes. Therefore, simultaneous detection of several inflammatory molecules in the early or pre-symptomatic stage may improve the early diagnosis of AD. Further studies are needed to determine, how induction or inhibition of inflammatory factors could be used for AD therapies. This review summarizes the role or possible role of immune cells and inflammatory molecules in disease progression or prevention.
... Several inflammatory molecules, such as interleukins, tumor necrosis factors were established as genetic risk factors for AD onset. This also suggested that S100A9 could be involved in dementia onset 11 . CR1 (Table 1. no. 3.) is located on chromosome 1, and it encodes the complement component (3b/4b) receptor 1 protein, which is a transmembrane glycoprotein. ...
... Several inflammatory molecules, such as interleukins, tumor necrosis factors were established as genetic risk factors for AD onset. This also suggested that S100A9 could be involved in dementia onset 11 . CR1 (Table 1. no. 3.) is located on chromosome 1, and it encodes the complement component (3b/4b) receptor 1 protein, which is a transmembrane glycoprotein. ...
... Several inflammatory molecules, such as interleukins, tumor necrosis factors were established as genetic risk factors for AD onset. This also suggested that S100A9 could be involved in dementia onset 11 . CR1 (Table 1. no. 3.) is located on chromosome 1, and it encodes the complement component (3b/4b) receptor 1 protein, which is a transmembrane glycoprotein. ...
Several types of neurodegenerative diseases were described, including Alzheimer’s disease (AD), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), prion disease, and Parkinson’s disease (PD). Since the potential treatment strategies of these disorders might be more successful in the pre-clinical stages than in the actual clinical setup, new diagnostic methods were needed. The involvement of heredity in neurodegenerative disorders was established, but several neurodegenerative disorders such as AD, PD, ALS, FTD and Huntington’s disease (HD) are highly complex. Sanger sequencing was used to detect mutations that are causative or risk factors for diseases. The problem with standard sequencing is its high cost and low speed. Recently, next generation sequencing (NGS) strategies were developed, which could provide a more complex genetic analysis of patients with neurodegenerative diseases. In this study, 50 genes were selected, which were established as causative genes for neurodegenerative diseases, but we also included several risk factor genes and candidate genes. Primers (maximum 400-bp length) were designed to screen for mutations and variants in them. We plan to use these primers for NGS screening to create a more detailed genetic profile for these patients. This study could enhance disease diagnosis and would be also helpful in estimating the risk for disease onset in the future. © 2015, The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Science+Business Media Dordrecht.
In this study, the effect of Phycocyanin (Pc) to ameliorate the cognitive dysfunction in experimental model of Alzheimer’s disease (AD) was evaluated. Intracerebroventricular (ICV) induction of Streptozotocin (STZ) (3 mg/kg) was done bilaterally twice in rats on alternative days. Rats were injected with Pc (50, 100 mg/kg; i.p.) for 28 days daily for behavioural and cholinergic activity assessment. As the effect was only significant at 100 mg/kg, later molecular experiments were performed using the same only. STZ induction led to increased activity of hippocampal cholinesterases and BAX and decreased activity of BCL-2 and ChAT. It enhanced TNF-α, and NF-κB in rat’s brain and reduced BDNF and IGF-1 levels. Dysfunctional insulin signaling and decreased gene expressions of PI3-K, AKT was also observed. However, Pc treatment significantly prevented STZ-induced increased activity of hippocampal cholinesterases and BAX as well as increased the levels of BCL-2 and ChAT. Neuroinflammation was significantly attenuated and BDNF and IGF-1 levels were upregulated. Further, Pc also alleviated dysfunctional insulin signaling as evidenced by increased gene expression of IRS-1, PI3-K, AKT. In conclusion, our study demonstrated the immense potential of Pc in attenuating STZ-induced cognitive decline and it may be further explored as a therapeutic agent in managing AD.
