scholarly journals Alzheimer’s Disease Results in Salivary Redox Imbalance Towards Oxidation Reactions

2021 ◽  
Author(s):  
Anna Zalewska ◽  
Anna Klimiuk ◽  
Sara Zięba ◽  
Olga Wnorowska ◽  
Małgorzata Rusak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nitrosative Stress ◽  
Redox Balance ◽  
Control Group ◽  
Enzymatic Antioxidants ◽  
Redox Imbalance ◽  
Saliva Secretion ◽  
Number Of Patients ◽  
Β Amyloid

Abstract Alzheimer’s disease (AD) is associated with the deposition of β-amyloid in the brain. AD accounts for over 50% of cases of dementia which results from disturbances in redox homeostasis. Indeed, increased intensity of protein oxidation and nitration as well as lipid peroxidation is observed in brain areas with considerable amounts of amyloid plaques and neurofibrillary tangles. However, little is known about the oxidoreductive balance of salivary glands in AD patients. Therefore, the aim of this study was to evaluate the antioxidant barrier and oxidative/nitrosative stress biomarkers in stimulated saliva and blood of AD patients. The study was participated by 25 AD patients and 25 non-demented controls without neurological diseases or cognitive impairment, matched by age and gender to the study group. The number of patients was determined based on a previous pilot study (test power = 0.9). We found a significant decrease in the activity of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx), increased activity of catalase (CAT) and reduced concentration of plasma non-enzymatic antioxidants (uric acid, UA and reduced glutathione, GSH). In contrast, in the stimulated saliva of AD patients we observed significantly decreased activity of all antioxidant enzymes (SOD, CAT and GPx) as well as concentration of GSH compared to the control group. The content of lipid (malondialdehyde, MDA) and protein (advanced oxidation protein products, AOPP; advanced glycation end-products, AGE) oxidation products as well as biomarkers of nitrosative stress (peroxynitrite, nitrotyrosine) was significantly higher in both saliva and plasma of AD patients compared to the controls. In AD patients, we also observed a considerable decrease in stimulated saliva secretion and salivary total protein content, and an increase in salivary β-amyloid concentration.In conclusion, AD results in redox imbalance towards oxidative reactions, both at the level of the oral cavity and the entire body. General redox balance disturbances do not coincide with salivary redox balance disturbances. Reduction in stimulated saliva secretion in AD patients reflects secretory dysfunction of the parotid glands.

scholarly journals Salivary gland dysfunction and salivary redox imbalance in patients with Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Zalewska ◽  
Anna Klimiuk ◽  
Sara Zięba ◽  
Olga Wnorowska ◽  
Małgorzata Rusak ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Nitrosative Stress ◽  
Redox Balance ◽  
Control Group ◽  
Enzymatic Antioxidants ◽  
Redox Imbalance ◽  
Saliva Secretion ◽  
Number Of Patients ◽  
Β Amyloid

AbstractAlzheimer’s disease (AD) is associated with the deposition of β-amyloid in the brain. AD accounts for over 50% of cases of dementia which results from disturbances in redox homeostasis. Indeed, increased intensity of protein oxidation and nitration as well as lipid peroxidation is observed in brain areas with considerable amounts of amyloid plaques and neurofibrillary tangles. However, little is known about the oxidoreductive balance of salivary glands in AD patients. Therefore, the aim of this study was to evaluate the antioxidant barrier and oxidative/nitrosative stress biomarkers in stimulated saliva and blood of AD patients. The study was participated by 25 AD patients and 25 non-demented controls without neurological diseases or cognitive impairment, matched by age and gender to the study group. The number of patients was determined based on a previous pilot study (test power = 0.9). We found a significant decrease in the activity of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GPx), increased activity of catalase (CAT) and reduced concentration of plasma non-enzymatic antioxidants (uric acid, UA and reduced glutathione, GSH). In contrast, in the stimulated saliva of AD patients we observed significantly decreased activity of all antioxidant enzymes (SOD, CAT and GPx) as well as concentration of GSH compared to the control group. The content of lipid (malondialdehyde, MDA) and protein (advanced oxidation protein products, AOPP; advanced glycation end-products, AGE) oxidation products as well as biomarkers of nitrosative stress (peroxynitrite, nitrotyrosine) was significantly higher in both saliva and plasma of AD patients compared to the controls. In AD patients, we also observed a considerable decrease in stimulated saliva secretion and salivary total protein content, and an increase in salivary β-amyloid concentration. In conclusion, AD results in redox imbalance towards oxidative reactions, both at the level of the oral cavity and the entire body. General redox balance disturbances do not coincide with salivary redox balance disturbances. Reduction in stimulated saliva secretion in AD patients reflects secretory dysfunction of the parotid glands.

Alzheimer’s Disease: Erythrocyte 2,3-diphosphoglycerate Content and Circulating Erythropoietin

2019 ◽  
Vol 16 (9) ◽  
pp. 834-835
Author(s):  
Petter Järemo ◽  
Alenka Jejcic ◽  
Vesna Jelic ◽  
Tasmin Shahnaz ◽  
Homira Behbahani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cell Damage ◽  
Control Group ◽  
Red Cell ◽  
Oxygen Release ◽  
Regulatory Pathways ◽  
Β Amyloid ◽  
2,3 Dpg

Background: Alzheimer’s Disease (AD) features the accumulation of β-amyloid in erythrocytes. The subsequent red cell damage may well affect their oxygen-carrying capabilities. 2,3- diphosphoglycerate (2,3-DPG) binds to the hemoglobin thereby promoting oxygen release. It is theorized that 2,3-DPG is reduced in AD and that the resulting hypoxia triggers erythropoietin (EPO) release. Methods & Objective: To explore this theory, we analyzed red cell 2,3-DPG content and EPO in AD, mild cognitive impairment, and the control group, subjective cognitive impairment. Results: We studied (i) 2,3-DPG in red cells, and (ii) circulating EPO in AD, and both markers were unaffected by dementia. Disturbances of these oxygen-regulatory pathways do not appear to participate in brain hypoxia in AD.

scholarly journals Ultrasound Mediated Microbubbles Destruction Assists Dual Delivery of Beta-amyloid Antibody and NSCs to Restore Neural Function in Transgenic Mice of Alzheimer’s Disease

2020 ◽  
Author(s):  
qiong Zhu ◽  
hai Cui ◽  
yiyi Liao ◽  
xue Guan ◽  
ying He ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Targeted Delivery ◽  
Function Evaluation ◽  
Control Group ◽  
Neural Function ◽  
Imaging Method ◽  
The Us ◽  
Β Amyloid

Abstract Background : To explore the feasibility, efficacy and safety of ultrasound mediated microbubbles destruction（UMMD） assisted dual delivery of β-amyloid antibody loaded by microbubbles (MB Aβ ) and neural stem cells (NSCs) on Alzheimer’s disease（AD）. Methods : 27 APP/PS1 double transgenic mice and 33 wild-type mice were used. The dual delivery of β-amyloid antibody and NSCs group (US+MB Aβ +NSCs), single delivery of β-amyloid antibody group (US+MB Aβ ), US+MB group, Control group and Wild group, were involved in the experiment. MB Aβ or MB were injected via the tail vein, followed by NSCs or saline administration and exposed to ultrasound once a week for four times. The survival of NSCs was detected with the in vivo imaging method. Mice in each group were used for behavioral function evaluation and the pathology tests. Brain samples were used to detect β-amyloid deposition, BDNF and synaptophysin expression. Results : BBB was opened by UMMD with an opening time about 10 h. The transplanted NSCs survived in AD brain for no more than 72 h. The learning and spatial memory function was significantly improved in the US+MB Aβ +NSCs group, US+MB Aβ group came second. Immunochemistry results showed amyloid plaques reduction in the US+MB Aβ +NSCs group at the cortex and hippocampus. Higher level of BDNF was demonstrated in the US+MB Aβ +NSCs group than the US+MB Aβ group and the Control group with Western Blot and immunofluorescence examination, but synaptophysin remained no significant changes. Conclusions : UMMD assisted combined delivery of β-amyloid antibody and NSCs to AD mice brain can help to clear the Aβ peptide, increase BDNF level and restore the impaired neural function, which was superior to β-amyloid antibody delivery group. Therefore, the combined targeted delivery assisted by UMMD strategy may be a promising and safe method on treating AD.

Biochemical investigations in patients with dementia

2002 ◽  
Vol 39 (3) ◽  
pp. 211-220 ◽  
Author(s):  
Alison Green
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Acetylcholinesterase Inhibitors ◽  
Amyloid Peptide ◽  
Number Of Patients ◽  
Diagnosis Of Dementia ◽  
Jakob Disease ◽  
Β Amyloid ◽  
Detection And Diagnosis ◽  
Β Amyloid Peptide

The recent development of acetylcholinesterase inhibitors to treat patients with Alzheimer's disease has increased interest in the use of biochemical markers for the early detection and diagnosis of dementia, but only the measurement of the protein 14-3-3 in cerebrospinal fluid (CSF) to help diagnose sporadic Creutzfeldt-Jakob disease has become accepted clinical practice. CSF concentrations of t protein and β-amyloid peptide 42 have been widely investigated as potential diagnostic tests for Alzheimer's disease, but neither has shown sufficient sensitivity and specificity for clinical use. Preliminary investigations suggest that β-amyloid peptide 42 may be useful in monitoring disease progression, but this needs to be verified. In addition, biochemical investigations may help to identify the small number of patients with treatable causes of dementia such as hypothyroidism and vitamin B12 deficiency, as well as any other compounding condition such as anaemia or diabetes mellitus that increase morbidity.

scholarly journals Insulin gene expression and functional activity of insulin signaling pathway in Alzheimer's disease

2021 ◽  
Vol 6 (4) ◽  
pp. 8-21
Author(s):  
Y. V. Gorina ◽  
E. D. Khilazheva ◽  
Yu. K. Komleva ◽  
O. L. Lopatina ◽  
A. B. Salmina
Keyword(s):  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Insulin Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Adapter Protein ◽  
Brain Areas ◽  
Model Of Alzheimer’S Disease ◽  
Β Amyloid

Aim. To study the insulin (INS) gene expression, insulin and lactate levels, expression of Fe65 adapter protein, and level of oxidative DNA damage marker γH2AX in different brain areas in the experimental model of Alzheimer's disease.Materials and Methods. Male, 4-month-old C57BL/6 mice received either intrahippocampal injection of β-amyloid (C57BL/6 + Aβ 1-42) or phosphate-buffered saline (C57BL/6 + PBS). Insulin (INS) gene expression in the hippocampus and amygdala was assessed by means of reverse transcription-polymerase chain reaction. Levels of lactate and insulin in different brain areas were measured by enzyme-linked immunosorbent assay. Expression of Fe65 adapter protein and γH2AX in the hippocampus was studied by immunofluorescence staining followed by confocal microscopy.Results. We found an overexpression of the INS gene in the hippocampus and amygdala, an increase in lactate level in the hippocampus, and slightly increased insulin level in the amygdala of mice with Alzheimer's disease as compared with the control group. Neurodegeneration was accompanied by an elevated endothelial expression of Fe65 adapter protein (p= 0.04) and γH2AX in hippocampal neurons (p = 0.04).Conclusion. Alzheimer's disease neurodegeneration is accompanied by a disrupted insulin signaling and impaired glucose metabolism in the hippocampus and amygdala. This further leads to a neuronal accumulation of γH2AX and impaired amyloid precursor protein proteolysis because of insulin inability to inhibit its interaction with the Fe65 adapter protein and to prevent formation and deposition of β-amyloid.

New strategies for diagnosis and treatment of Alzheimer's disease: monoclonal antibodies to beta-amyloid

2019 ◽  
Vol 1 (2) ◽  
pp. 35-42 ◽  
Author(s):  
A. A. Pilipovich ◽  
A. B. Danilov
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Monoclonal Antibodies ◽  
Pathological Process ◽  
Number Of Patients ◽  
Β Amyloid ◽  
Near Future ◽  
Ad Therapy ◽  
Timely Treatment ◽  
New Strategies

Alzheimer's disease (AD) is a progressive neurodegenerative disease that is the most common cause of dementia. Currently, there are about 46.8 million people with asthma in the world. It is believed that the number of patients with BA doubles almost every 20 years, and the issue of timely treatment and prolongation of the active life of these patients is becoming ever more acute. Nowdays only five drugs have been approved for the treatment of asthma, they include cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists (memantine). Unfortunately, their use provides tempora/y and incomplete symptomatic effect, can be accompanied by side effects and does not shw down the progression of asthma, therefore the development of drugs for more effective treatment of asthma is extremely important. Laboratory and clinical studies suggest that in the near future, AD-therapy will become more focused on disease modification and it is likely that AD will be successfully treated even before significant cognitive impairment develops, at the presymptom-atic or preclinical stages. The main therapeutic goal of these studies is the treatment of the pathological process (reduction of β-amyloidosis or reduction of the formation of neurofibrillaiy tangles) to prevent subsequent neurodegeneration and possible cognitive decline. Currently, despite all sorts of problems, immunotherapy with the introduction of monoclonal antibodies to β-amyloid is considered one of the most promising approaches to reducing the degree of neurodegeneration.

Аnticholinesterase and antioxidant activity of new binary conjugates of (с)-carbolines

2019 ◽  
Vol 484 (1) ◽  
pp. 104-108
Author(s):  
G. F. Makhaeva ◽  
E. F. Shevtsova ◽  
N. P. Boltneva ◽  
N. V. Kovaleva ◽  
E. V. Rudakova ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Antioxidant Activity ◽  
Anticholinesterase Activity ◽  
Amyloid Aggregation ◽  
Varying Length ◽  
Β Amyloid ◽  
New Compounds

This study presents the synthesis of binary tetrohydro-γ-carbolines with ditriazol spacers of varying length, which exhibit anticholinesterase and antioxidant activity, as compared to the original Dimebon prototype. Anticholinesterase activity suggests the potential ability of the new compounds to block β-amyloid aggregation induced by anticholinesterase, making them promising candidates for further research preparations for the treatment of Alzheimer's disease. Particular attention should be paid to the conjugate with an intertriazol hexamethylene spacer, which can be regarded as the leading compound in this series.

Synthesis of a Novel Curcumin Derivative as a Potential Imaging Probe in Alzheimer’s Disease Imaging

2019 ◽  
Vol 16 (8) ◽  
pp. 723-731 ◽  
Author(s):  
Alexander Sturzu ◽  
Sumbla Sheikh ◽  
Hubert Kalbacher ◽  
Thomas Nägele ◽  
Christopher Weidenmaier ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Flow Cytometry ◽  
Transgenic Mice ◽  
Ex Vivo ◽  
Amyloid Plaques ◽  
Laser Scanning Microscopy ◽  
Β Amyloid ◽  
Curcumin Derivative

Background: Curcumin has been of interest in the field of Alzheimer’s disease. Early studies on transgenic mice showed promising results in the reduction of amyloid plaques.However, curcumin is very poorly soluble in aqueous solutions and not easily accessible to coupling as it contains only phenolic groups as potential coupling sites. For these reasons only few imaging studies using curcumin bound as an ester were performed and curcumin is mainly used as nutritional supplement. Methods: In the present study we produced an aminoethyl ether derivative of curcumin using a nucleophilic substitution reaction. This is a small modification and should not impact the properties of curcumin while introducing an easily accessible reactive amino group. This novel compound could be used to couple curcumin to other molecules using the standard methods of peptide synthesis. We studied the aminoethyl-curcumin compound and a tripeptide carrying this aminoethyl-curcumin and the fluorescent dye fluorescein (FITC-curcumin) in vitro on cell culture using confocal laser scanning microscopy and flow cytometry. Then these two substances were tested ex vivo on brain sections prepared from transgenic mice depicting Alzheimer-like β-amyloid plaques. Results: In the in vitro CLSM microscopy and flow cytometry experiments we found dot-like unspecific uptake and only slight cytotoxicity correlating with this uptake. As these measurements were optimized for the use of fluorescein as dye we found that the curcumin at 488nm fluorescence excitation was not strong enough to use it as a fluorescence marker in these applications. In the ex vivo sections CLSM experiments both the aminoethyl-curcumin and the FITC-curcumin peptide bound specifically to β- amyloid plaques. Conclusion: In conclusion we successfully produced a novel curcumin derivative which could easily be coupled to other imaging or therapeutic molecules as a sensor for amyloid plaques.

MiR-335-5p Inhibits β-Amyloid (Aβ) Accumulation to Attenuate Cognitive Deficits Through Targeting c-jun-N-terminal Kinase 3 in Alzheimer’s Disease

2020 ◽  
Vol 17 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Dan Wang ◽  
Zhifu Fei ◽  
Song Luo ◽  
Hai Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transgenic Mice ◽  
Western Blot ◽  
Mrna Expression ◽  
Cognitive Deficits ◽  
Protein Levels ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
The Relationship

Objectives: Alzheimer's disease (AD), also known as senile dementia, is a common neurodegenerative disease characterized by progressive cognitive impairment and personality changes. Numerous evidences have suggested that microRNAs (miRNAs) are involved in the pathogenesis and development of AD. However, the exact role of miR-335-5p in the progression of AD is still not clearly clarified. Methods: The protein and mRNA levels were measured by western blot and RNA extraction and quantitative real-time PCR (qRT-PCR), respectively. The relationship between miR-335-5p and c-jun-N-terminal kinase 3 (JNK3) was confirmed by dual-luciferase reporter assay. SH-SY5Y cells were transfected with APP mutant gene to establish the in vitro AD cell model. Flow cytometry and western blot were performed to evaluate cell apoptosis. The APP/PS1 transgenic mice were used as an in vivo AD model. Morris water maze test was performed to assess the effect of miR- 335-5p on the cognitive deficits in APP/PS1 transgenic mice. Results: The JNK3 mRNA expression and protein levels of JNK3 and β-Amyloid (Aβ) were significantly up-regulated, and the mRNA expression of miR-335-5p was down-regulated in the brain tissues of AD patients. The expression levels of miR-335-5p and JNK3 were significantly inversely correlated. Further, the dual Luciferase assay verified the relationship between miR-335- 5p and JNK3. Overexpression of miR-335-5p significantly decreased the protein levels of JNK3 and Aβ and inhibited apoptosis in SH-SY5Y/APPswe cells, whereas the inhibition of miR-335-5p obtained the opposite results. Moreover, the overexpression of miR-335-5p remarkably improved the cognitive abilities of APP/PS1 mice. Conclusion: The results revealed that the increased JNK3 expression, negatively regulated by miR-335-5p, may be a potential mechanism that contributes to Aβ accumulation and AD progression, indicating a novel approach for AD treatment.

Identify Compounds' Target Against Alzheimer's Disease Based on In-Silico Approach

2019 ◽  
Vol 16 (3) ◽  
pp. 193-208 ◽  
Author(s):  
Yan Hu ◽  
Guangya Zhou ◽  
Chi Zhang ◽  
Mengying Zhang ◽  
Qin Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecule ◽  
Characteristic Curve ◽  
Machine Learning Algorithms ◽  
Learner Model ◽  
Mao B ◽  
Number Of Patients ◽  
Sar Model ◽  
Set Up

Background: Alzheimer's disease swept every corner of the globe and the number of patients worldwide has been rising. At present, there are as many as 30 million people with Alzheimer's disease in the world, and it is expected to exceed 80 million people by 2050. Consequently, the study of Alzheimer’s drugs has become one of the most popular medical topics. Methods: In this study, in order to build a predicting model for Alzheimer’s drugs and targets, the attribute discriminators CfsSubsetEval, ConsistencySubsetEval and FilteredSubsetEval are combined with search methods such as BestFirst, GeneticSearch and Greedystepwise to filter the molecular descriptors. Then the machine learning algorithms such as BayesNet, SVM, KNN and C4.5 are used to construct the 2D-Structure Activity Relationship(2D-SAR) model. Its modeling results are utilized for Receiver Operating Characteristic curve(ROC) analysis. Results: The prediction rates of correctness using Randomforest for AChE, BChE, MAO-B, BACE1, Tau protein and Non-inhibitor are 77.0%, 79.1%, 100.0%, 94.2%, 93.2% and 94.9%, respectively, which are overwhelming as compared to those of BayesNet, BP, SVM, KNN, AdaBoost and C4.5. Conclusion: In this paper, we conclude that Random Forest is the best learner model for the prediction of Alzheimer’s drugs and targets. Besides, we set up an online server to predict whether a small molecule is the inhibitor of Alzheimer's target at http://47.106.158.30:8080/AD/. Furthermore, it can distinguish the target protein of a small molecule.

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