scholarly journals SARS-CoV-2 Exacerbates Beta-Amyloid Neurotoxicity, Inflammation and Oxidative Stress in Alzheimer’s Disease Patients

2021 ◽  
Vol 22 (24) ◽  
pp. 13603
Author(s):  
Luigi Chiricosta ◽  
Agnese Gugliandolo ◽  
Emanuela Mazzon
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Immune Response ◽  
Beta Amyloid ◽  
The Elderly ◽  
Gene Expression Omnibus ◽  
Brain Organization ◽  
And Control ◽  
And Oxidative Stress

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the pandemic Coronavirus Disease 19 (COVID-19), causing millions of deaths. The elderly and those already living with comorbidity are likely to die after SARS-CoV-2 infection. People suffering from Alzheimer’s disease (AD) have a higher risk of becoming infected, because they cannot easily follow health roles. Additionally, those suffering from dementia have a 40% higher risk of dying from COVID-19. Herein, we collected from Gene Expression Omnibus repository the brain samples of AD patients who died of COVID-19 (AD+COVID-19), AD without COVID-19 (AD), COVID-19 without AD (COVID-19) and control individuals. We inspected the transcriptomic and interactomic profiles by comparing the COVID-19 cohort against the control cohort and the AD cohort against the AD+COVID-19 cohort. SARS-CoV-2 in patients without AD mainly activated processes related to immune response and cell cycle. Conversely, 21 key nodes in the interactome are deregulated in AD. Interestingly, some of them are linked to beta-amyloid production and clearance. Thus, we inspected their role, along with their interactors, using the gene ontologies of the biological process that reveals their contribution in brain organization, immune response, oxidative stress and viral replication. We conclude that SARS-CoV-2 worsens the AD condition by increasing neurotoxicity, due to higher levels of beta-amyloid, inflammation and oxidative stress.

Alpha-1-Antichymotrypsin: a Common Player for Type 2 Diabetes and Alzheimer's Disease

2020 ◽  
Vol 16 ◽  
Author(s):  
Nataly Guzmán-Herrera ◽  
Viridiana C. Pérez-Nájera ◽  
Luis A. Salazar-Olivo
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Type 2 Diabetes ◽  
Alzheimer's Disease ◽  
Regulatory Networks ◽  
Therapeutic Strategies ◽  
Oxidative Stresses ◽  
Bibliographic Search ◽  
And Oxidative Stress

Background: Numerous studies have shown a significant association between type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD), two pathologies affecting millions of people worldwide. Chronic inflammation and oxidative stress are two conditions common to these diseases also affecting the activity of the serpin alpha-1-antichymotrypsin (ACT), but a possible common role for this serpin in T2D and AD remains unclear. Objective: To explore the possible regulatory networks linking ACT to T2D and AD. Materials and Methods: A bibliographic search was carried out in PubMed, Med-line, Open-i, ScienceDirect, Scopus and SpringerLink for data indicating or suggesting association among T2D, AD, and ACT. Searched terms like “alpha-1-antichymotrypsin”, “type 2 diabetes”, “Alzheimer's disease”, “oxidative stress”, “pro-inflammatory mediators” among others were used. Moreover, common therapeutic strategies between T2D and AD as well as the use of ACT as a therapeutic target for both diseases were included. Results: ACT has been linked with development and maintenance of T2D and AD and studies suggest their participation through activation of inflammatory pathways and oxidative stress, mechanisms also associated with both diseases. Likewise, evidences indicate that diverse therapeutic approaches are common to both diseases. Conclusion: Inflammatory and oxidative stresses constitute a crossroad for T2D and AD where ACT could play an important role. In-depth research on ACT involvement in these two dysfunctions could generate new therapeutic strategies for T2D and AD.

scholarly journals Antia, a Natural Antioxidant Product, Attenuates Cognitive Dysfunction in Streptozotocin-Induced Mouse Model of Sporadic Alzheimer’s Disease by Targeting the Amyloidogenic, Inflammatory, Autophagy, and Oxidative Stress Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Nesrine S. El Sayed ◽  
Mamdooh H. Ghoneum
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Protective Effect ◽  
Cognitive Dysfunction ◽  
Protective Role ◽  
Sporadic Alzheimer’S Disease ◽  
Stat3 Pathway ◽  
And Oxidative Stress

Background. Many neurodegenerative diseases such as Alzheimer’s disease are associated with oxidative stress. Therefore, antioxidant therapy has been suggested for the prevention and treatment of neurodegenerative diseases. Objective. We investigated the ability of the antioxidant Antia to exert a protective effect against sporadic Alzheimer’s disease (SAD) induced in mice. Antia is a natural product that is extracted from the edible yamabushitake mushroom, the gotsukora and kothala himbutu plants, diosgenin (an extract from wild yam tubers), and amla (Indian gooseberry) after treatment with MRN-100. Methods. Single intracerebroventricular (ICV) injection of streptozotocin (STZ) (3 mg/kg) was used for induction of SAD in mice. Antia was injected intraperitoneally (i.p.) in 3 doses (25, 50, and 100 mg/kg/day) for 21 days. Neurobehavioral tests were conducted within 24 h after the last day of injection. Afterwards, mice were sacrificed and their hippocampi were rapidly excised, weighed, and homogenized to be used for measuring biochemical parameters. Results. Treatment with Antia significantly improved mice performance in the Morris water maze. In addition, biochemical analysis showed that Antia exerted a protective effect for several compounds, including GSH, MDA, NF-κB, IL-6, TNF-α, and amyloid β. Further studies with western blot showed the protective effect of Antia for the JAK2/STAT3 pathway. Conclusions. Antia exerts a significant protection against cognitive dysfunction induced by ICV-STZ injection. This effect is achieved through targeting of the amyloidogenic, inflammatory, and oxidative stress pathways. The JAK2/STAT3 pathway plays a protective role for neuroinflammatory and neurodegenerative diseases such as SAD.

scholarly journals Correlative Microscopy to Localize and Characterize Iron Deposition in Alzheimer’s Disease

2020 ◽  
Vol 4 (1) ◽  
pp. 525-536
Author(s):  
Steven J. Madsen ◽  
Phillip S. DiGiacomo ◽  
Yitian Zeng ◽  
Maged Goubran ◽  
Yuanxin Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Electron Microscope ◽  
Oxidation State ◽  
Transmission Electron Microscope ◽  
Iron Deposition ◽  
Direct Link ◽  
Transmission Electron ◽  
And Oxidative Stress

Background: Recent evidence suggests that the accumulation of iron, specifically ferrous Fe2+, may play a role in the development and progression of neurodegeneration in Alzheimer’s disease (AD) through the production of oxidative stress. Objective: To localize and characterize iron deposition and oxidation state in AD, we analyzed human hippocampal autopsy samples from four subjects with advanced AD that have been previously characterized with correlative MRI-histology. Methods: We perform scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and electron energy loss spectroscopy (EELS) in the higher resolution transmission electron microscope on the surface and cross-sections of specific iron-rich regions of interest. Results: Specific previously analyzed regions were visualized using SEM and confirmed to be iron-rich deposits using EDS. Subsequent analysis using focused ion beam cross-sectioning and SEM characterized the iron deposition throughout the 3-D volumes, confirming the presence of iron throughout the deposits, and in two out of four specimens demonstrating colocalization with zinc. Analysis of traditional histology slides showed the analyzed deposits overlapped both with amyloid and tau deposition. Following higher resolution analysis of a single iron deposit using scanning transmission electron microscope (STEM), we demonstrated the potential of monochromated STEM-EELS to discern the relative oxidation state of iron within a deposit. Conclusion: These findings suggest that iron is present in the AD hippocampus and can be visualized and characterized using combined MRI and EM techniques. An altered relative oxidation state may suggest a direct link between iron and oxidative stress in AD. These methods thus could potentially measure an altered relative oxidation state that could suggest a direct link between iron and oxidative stress in AD. Furthermore, we have demonstrated the ability to analyze metal deposition alongside commonly used histological markers of AD pathology, paving the way for future insights into the molecular interactions between Aβ, tau, iron, and other putative metals, such as zinc.

A multifunctional compound ebselen reverses memory impairment, apoptosis and oxidative stress in a mouse model of sporadic Alzheimer's disease

2019 ◽  
Vol 109 ◽  
pp. 107-117 ◽  
Author(s):  
Franciele Martini ◽  
Suzan Gonçalves Rosa ◽  
Isabella Pregardier Klann ◽  
Bruna Cruz Weber Fulco ◽  
Fabiano Barbosa Carvalho ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Memory Impairment ◽  
Sporadic Alzheimer’S Disease ◽  
And Oxidative Stress

scholarly journals Antidiabetic Drugs in Alzheimer’s Disease: Mechanisms of Action and Future Perspectives

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Grazia Daniela Femminella ◽  
Leonardo Bencivenga ◽  
Laura Petraglia ◽  
Lucia Visaggi ◽  
Lucia Gioia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
The Elderly ◽  
Mechanisms Of Action ◽  
Antidiabetic Drugs ◽  
Common Mechanism ◽  
Public Health Burden ◽  
Preclinical And Clinical Studies ◽  
And Oxidative Stress ◽  
Potential Use

Diabetes mellitus (DM) and Alzheimer’s disease (AD) are two highly prevalent conditions in the elderly population and major public health burden. In the past decades, a pathophysiological link between DM and AD has emerged and central nervous system insulin resistance might play a significant role as a common mechanism; however, other factors such as inflammation and oxidative stress seem to contribute to the shared pathophysiological link. Both preclinical and clinical studies have evaluated the possible neuroprotective mechanisms of different classes of antidiabetic medications in AD, with some promising results. Here, we review the evidence on the mechanisms of action of antidiabetic drugs and their potential use in AD.

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