scholarly journals Oxidative Stress: A Key Modulator in Neurodegenerative Diseases

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1583 ◽  
Author(s):  
Anju Singh ◽  
Ritushree Kukreti ◽  
Luciano Saso ◽  
Shrikant Kukreti
Keyword(s):  
Oxidative Stress ◽  
Oxidative Phosphorylation ◽  
Neurodegenerative Diseases ◽  
Apoptotic Cell ◽  
Regulatory Element ◽  
Phospholipid Metabolism ◽  
Hydroxyl Free Radical ◽  
Neuronal Membranes ◽  
Long Time ◽  
Atp Supply

Oxidative stress is proposed as a regulatory element in ageing and various neurological disorders. The excess of oxidants causes a reduction of antioxidants, which in turn produce an oxidation–reduction imbalance in organisms. Paucity of the antioxidant system generates oxidative-stress, characterized by elevated levels of reactive species (oxygen, hydroxyl free radical, and so on). Mitochondria play a key role in ATP supply to cells via oxidative phosphorylation, as well as synthesis of essential biological molecules. Various redox reactions catalyzed by enzymes take place in the oxidative phosphorylation process. An inefficient oxidative phosphorylation may generate reactive oxygen species (ROS), leading to mitochondrial dysfunction. Mitochondrial redox metabolism, phospholipid metabolism, and proteolytic pathways are found to be the major and potential source of free radicals. A lower concentration of ROS is essential for normal cellular signaling, whereas the higher concentration and long-time exposure of ROS cause damage to cellular macromolecules such as DNA, lipids and proteins, ultimately resulting in necrosis and apoptotic cell death. Normal and proper functioning of the central nervous system (CNS) is entirely dependent on the chemical integrity of brain. It is well established that the brain consumes a large amount of oxygen and is highly rich in lipid content, becoming prone to oxidative stress. A high consumption of oxygen leads to excessive production of ROS. Apart from this, the neuronal membranes are found to be rich in polyunsaturated fatty acids, which are highly susceptible to ROS. Various neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), among others, can be the result of biochemical alteration (due to oxidative stress) in bimolecular components. There is a need to understand the processes and role of oxidative stress in neurodegenerative diseases. This review is an effort towards improving our understanding of the pivotal role played by OS in neurodegenerative disorders.

scholarly journals Ginkgo biloba Prevents Oxidative Stress-Induced Apoptosis Blocking p53 Activation in Neuroblastoma Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 279 ◽  
Author(s):  
Francesco Di Meo ◽  
Rossana Cuciniello ◽  
Sabrina Margarucci ◽  
Paolo Bergamo ◽  
Orsolina Petillo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Ginkgo Biloba ◽  
Apoptotic Cell ◽  
Neuroblastoma Cells ◽  
Apoptotic Cell Death ◽  
Parp Cleavage ◽  
Egb 761 ◽  
Induced Apoptosis

Oxidative stress has been associated to neuronal cell loss in neurodegenerative diseases. Neurons are post-mitotic cells that are very sensitive to oxidative stress—especially considering their limited capacity to be replaced. Therefore, reduction of oxidative stress, and inhibiting apoptosis, will potentially prevent neurodegeneration. In this study, we investigated the neuroprotective effect of Ginkgo biloba extract (EGb 761) against H2O2 induced apoptosis in SK-N-BE neuroblastoma cells. We analysed the molecular signalling pathway involved in the apoptotic cell death. H2O2 induced an increased acetylation of p53 lysine 382, a reduction in mitochondrial membrane potential, an increased BAX/Bcl-2 ratio and consequently increased Poly (ADP-ribose) polymerase (PARP) cleavage. All these effects were blocked by EGb 761 treatment. Thus, EGb 761, acting as intracellular antioxidant, protects neuroblastoma cells against activation of p53 mediated pathway and intrinsic mitochondrial apoptosis. Our results suggest that EGb 761, protecting against oxidative-stress induced apoptotic cell death, could potentially be used as nutraceutical for the prevention and treatment of neurodegenerative diseases.

scholarly journals Combined Inhibition of CXCR4 Signaling and System xc- Transporter Activity Induces Synthetic Lethality in T-ALL Cells By Suppressing Gsh and Inducing Ferroptosis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-37
Author(s):  
Jun Xia ◽  
Stephanie Sun ◽  
Matthew RM Jotte ◽  
Geoffrey L Uy ◽  
Ella Sorani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Oxidative Phosphorylation ◽  
Molecular Mechanisms ◽  
Synthetic Lethality ◽  
Reduced Glutathione ◽  
Apoptotic Cell ◽  
Lymphoblastic Leukemia ◽  
Cxcr4 Signaling ◽  
The Media

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that accounts for 10-15% of pediatric and 25% of adult ALL cases. Prior studies have established that most cases pf T-ALL are addicted to CXCR4 signaling. Indeed, strong preclinical data demonstrating therapeutic activity of BL-8040, a potent CXCR4 antagonist, have led to a clinical trial of BL-8040 in combination with nelarabine for patients with relapsed/refractory T-ALL (NCT02763384). However, the molecular mechanisms by which CXCR4 blockade induces T-ALL cell death are unknown. Using a human T-ALL xenotransplantation model, we previously reported that treatment with BL-8040 killed T-ALL cells through a non-apoptotic mechanism. Transcriptome sequencing revealed that BL-8040 induced alterations in genes involved in oxidative phosphorylation and carbohydrate metabolism. Indeed, seahorse experiments show that BL-8040 markedly reduced both oxidative phosphorylation and glycolysis. However, metabolic tracing studies using 13C-labeled glucose show that BL-8040 treatment does not have a major effect on the contribution of glucose to either glycolysis or the citric acid cycle. Instead, the major alteration observed is the reduced entry of glucose into the pentose phosphate pathway (PPP). A major function of the PPP pathway is to generate NADPH, which regulates reactive oxygen species (ROS) by producing reduced glutathione (GSH). Indeed, BL-8040 treatment resulted in a significant decrease in the ratio of reduced glutathione to oxidized glutathione. Together, these data suggest that BL-8040 induces oxidative stress by inhibiting GSH production. One mechanism utilized by cancer cells to regulate GSH levels and oxidative stress is the system xc- amino acid antiporter that mediates the exchange of extracellular L-cystine and intracellular l-glutamate across the plasma membrane, resulting in the production of GSH and oxidative protection. We measured L-cystine levels in the media of T-ALL cells cultured for 24 hours with or without BL-8040. A significant decrease in L-cystine in the media was observed. These data, along with increased expression of the xc- transporter (SLC7A11), suggested that increased system xc- activity was compensating for the loss of GSH induced by BL-8040. To test this possibility, we cultured T-ALL cells in L-cystine deficient media. Loss of L-cystine in the media resulted in a modest decrease in T-ALL cell viability that was markedly increased, in a synergistic fashion, upon treatment with BL-8040. Interestingly, caspase 3 was not activated, suggesting that, similar to in vivo results, BL-8040 induces a non-apoptotic cell death. This observation, coupled with the reduction in GSH, suggested the hypothesis that BL-8040 induces ferroptosis. Consistent with the hypothesis, treatment of T-ALL cells with ACXT-3102, a novel system xc- inhibitor, significantly enhanced BL-8040 killing of T-ALL cells in vitro. Collectively, these data suggest that T-ALL cells are sensitive to perturbations of the glutathione axis. Combined inhibition of CXCR4 signaling and system xc- activity exploits this vulnerability and presents a promising new therapeutic approach for T-ALL. Disclosures Uy: Astellas Pharma: Honoraria; Jazz Pharmaceuticals: Consultancy; Genentech: Consultancy; Agios: Consultancy; Pfizer: Consultancy; Daiichi Sankyo: Consultancy. Sorani:BiolineRx Ltd: Current Employment. Vainstein:BiolineRx Ltd: Current Employment. Davish:BiolineRx Ltd: Current Employment. Hawkins:Accuronix Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Association of Oxidative Stress with Neurological Disorders

2021 ◽  
Vol 19 ◽  
Author(s):  
Waseem Hassan ◽  
Hamsa Noreen ◽  
Shakila Rehman ◽  
Mohammad Amjad Kamal ◽  
Joao Batista Teixeira da Rocha
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Free Radicals ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Biological Effects ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Neuronal Membranes

Background: Oxidative stress is one of the main contributing factors involved in cerebral biochemical impairment. The higher susceptibility of the central nervous system to reactive oxygen species mediated damage could be attributed to several factors. For example, neurons use a greater quantity of oxygen, many parts of the brain have higher concentraton of iron, and neuronal mitochondria produce huge content of hydrogen peroxide. In addition, neuronal membranes have polyunsaturated fatty acids, which are predominantly vulnerable to oxidative stress (OS). OS is the imbalance between reactive oxygen species generation and cellular antioxidant potential. This may lead to various pathological conditions and diseases, especially neurodegenerative diseases such as, Parkinson’s, Alzheimer’s, and Huntington’s diseases. Objectives: In this study, we explored the involvement of OS in neurodegenerative diseases. Methods: We used different search terms like “oxidative stress and neurological disorders” “free radicals and neurodegenerative disorders” “oxidative stress, free radicals, and neurological disorders” and “association of oxidative stress with the name of disorders taken from the list of neurological disorders. We tried to summarize the source, biological effects, and physiologic functions of ROS. Results: Finally, it was noted that more than 190 neurological disorders are associated with oxidative stress.

Oxidative Stress and Neurodegenerative Diseases: Looking for a Therapeutic Solution Inspired on Benzopyran Chemistry

2015 ◽  
Vol 15 (5) ◽  
pp. 432-445 ◽  
Author(s):  
Alexandra Gaspar ◽  
Nuno Milhazes ◽  
Lourdes Santana ◽  
Eugenio Uriarte ◽  
Fernanda Borges ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases

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 Effect of Antioxidant Therapy on Oxidative Stress In Vivo

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 344
Author(s):  
Anna Maria Fratta Pasini ◽  
Luciano Cominacini
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Neurodegenerative Diseases ◽  
Antioxidant Therapy ◽  
Potential Benefits

Over the last few decades, many efforts have been put into fields that explore the potential benefits of antioxidants, especially with regards to aging, cancer, cardiovascular diseases, and neurodegenerative diseases. [...]

scholarly journals Mitochondria-Targeted Antioxidants: Future Perspectives in Kidney Ischemia Reperfusion Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Aleksandra Kezic ◽  
Ivan Spasojevic ◽  
Visnja Lezaic ◽  
Milica Bajcetic
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Current Status ◽  
Long Time ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Kidney Ischemia

Kidney ischemia/reperfusion injury emerges in various clinical settings as a great problem complicating the course and outcome. Ischemia/reperfusion injury is still an unsolved puzzle with a great diversity of investigational approaches, putting the focus on oxidative stress and mitochondria. Mitochondria are both sources and targets of ROS. They participate in initiation and progression of kidney ischemia/reperfusion injury linking oxidative stress, inflammation, and cell death. The dependence of kidney proximal tubule cells on oxidative mitochondrial metabolism makes them particularly prone to harmful effects of mitochondrial damage. The administration of antioxidants has been used as a way to prevent and treat kidney ischemia/reperfusion injury for a long time. Recently a new method based on mitochondria-targeted antioxidants has become the focus of interest. Here we review the current status of results achieved in numerous studies investigating these novel compounds in ischemia/reperfusion injury which specifically target mitochondria such as MitoQ, Szeto-Schiller (SS) peptides (Bendavia), SkQ1 and SkQR1, and superoxide dismutase mimics. Based on the favorable results obtained in the studies that have examined myocardial ischemia/reperfusion injury, ongoing clinical trials investigate the efficacy of some novel therapeutics in preventing myocardial infarct. This also implies future strategies in preventing kidney ischemia/reperfusion injury.

scholarly journals Dibenzoylthiamine Has Powerful Antioxidant and Anti-Inflammatory Properties in Cultured Cells and in Mouse Models of Stress and Neurodegeneration

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 361
Author(s):  
Margaux Sambon ◽  
Anna Gorlova ◽  
Alice Demelenne ◽  
Judit Alhama-Riba ◽  
Bernard Coumans ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Cell Line ◽  
Mouse Models ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Motor Dysfunction ◽  
Oxidative Stress Marker ◽  
Bv2 Cells ◽  
Anti Inflammatory

Thiamine precursors, the most studied being benfotiamine (BFT), have protective effects in mouse models of neurodegenerative diseases. BFT decreased oxidative stress and inflammation, two major characteristics of neurodegenerative diseases, in a neuroblastoma cell line (Neuro2a) and an immortalized brain microglial cell line (BV2). Here, we tested the potential antioxidant and anti-inflammatory effects of the hitherto unexplored derivative O,S-dibenzoylthiamine (DBT) in these two cell lines. We show that DBT protects Neuro2a cells against paraquat (PQ) toxicity by counteracting oxidative stress at low concentrations and increases the synthesis of reduced glutathione and NADPH in a Nrf2-independent manner. In BV2 cells activated by lipopolysaccharides (LPS), DBT significantly decreased inflammation by suppressing translocation of NF-κB to the nucleus. Our results also demonstrate the superiority of DBT over thiamine and other thiamine precursors, including BFT, in all of the in vitro models. Finally, we show that the chronic administration of DBT arrested motor dysfunction in FUS transgenic mice, a model of amyotrophic lateral sclerosis, and it reduced depressive-like behavior in a mouse model of ultrasound-induced stress in which it normalized oxidative stress marker levels in the brain. Together, our data suggest that DBT may have therapeutic potential for brain pathology associated with oxidative stress and inflammation by novel, coenzyme-independent mechanisms.

scholarly journals A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 539
Author(s):  
Santa Cirmi ◽  
Alessandro Maugeri ◽  
Giovanni Enrico Lombardo ◽  
Caterina Russo ◽  
Laura Musumeci ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Dopaminergic Neurons ◽  
Specific Interaction ◽  
Food Sources ◽  
Human Neuroblastoma Cell ◽  
Neuroprotective Effects ◽  
Human Neuroblastoma ◽  
Mandarin Juice

Parkinson’s disease (PD) is a degenerative disorder of the nervous system due to unceasing impairment of dopaminergic neurons situated in the substantia nigra. At present, anti-PD drugs acting on dopamine receptors are mainly symptomatic and have only very limited neuroprotective effects, whereas drugs slowing down neurodegeneration of dopaminergic neurons and deterioration of clinical symptoms are not yet available. Given that, the development of more valuable pharmacological strategies is highly demanded. Comprehensive research on innovative neuroprotective drugs has proven that anti-inflammatory and antioxidant molecules from food sources may prevent and/or counteract neurodegenerative diseases, such as PD. The present study was aimed at the evaluation the protective effect of mandarin juice extract (MJe) against 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma cell death. Treatment of differentiated SH-SY5Y cells with 6-OHDA brought cell death, and specifically, apoptosis, which was significantly inhibited by the preincubation with MJe through caspase 3 blockage and the modulation of p53, Bax, and Bcl-2 genes. In addition, it showed antioxidant properties in abiotic models as well as in vitro, where it reduced both reactive oxygen and nitrogen species induced by 6-OHDA, along with restored mitochondrial membrane potential, and prevented the oxidative DNA damage evoked by 6-OHDA. Furthermore, MJe restored the impaired balance of SNCA, LRRK2, PINK1, parkin, and DJ-1 gene levels, PD-related factors, caused by 6-OHDA oxidative stress. Overall, these results indicate that MJe exerts neuroprotective effects against 6-OHDA-induced cell death in SH-SY5Y cells by mechanisms involving both the specific interaction with intracellular pathways and its antioxidant capability. Our study suggests a novel possible strategy to prevent and/or ameliorate neurodegenerative diseases, such as PD.

scholarly journals Overexpression of Transcripts Coding for Renin-b but Not for Renin-a Reduce Oxidative Stress and Increase Cardiomyoblast Survival under Starvation Conditions

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1204
Author(s):  
Heike Wanka ◽  
Philipp Lutze ◽  
Alexander Albers ◽  
Janine Golchert ◽  
Doreen Staar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
B Cells ◽  
Apoptotic Cell ◽  
Renin Angiotensin System ◽  
Glucose Deprivation ◽  
Protective Effects ◽  
Glucose Depletion ◽  
A Cells ◽  
Apoptosis And Necrosis

A stimulated renin-angiotensin system is known to promote oxidative stress, apoptosis, necrosis and fibrosis. Renin transcripts (renin-b; renin-c) encoding a cytosolic renin isoform have been discovered that may in contrast to the commonly known secretory renin (renin-a) exert protective effects Here, we analyzed the effect of renin-a and renin-b overexpression in H9c2 cardiomyoblasts on apoptosis and necrosis as well as on potential mechanisms involved in cell death processes. To mimic ischemic conditions, cells were exposed to glucose starvation, anoxia or combined oxygen–glucose deprivation (OGD) for 24 h. Under OGD, control cells exhibited markedly increased necrotic and apoptotic cell death accompanied by enhanced ROS accumulation, loss of mitochondrial membrane potential and decreased ATP levels. The effects of OGD on necrosis were exaggerated in renin-a cells, but markedly diminished in renin-b cells. However, with respect to apoptosis, the effects of OGD were almost completely abolished in renin-b cells but interestingly also moderately diminished in renin-a cells. Under glucose depletion we found opposing responses between renin-a and renin-b cells; while the rate of necrosis and apoptosis was aggravated in renin-a cells, it was attenuated in renin-b cells. Based on our results, strategies targeting the regulation of cytosolic renin-b as well as the identification of pathways involved in the protective effects of renin-b may be helpful to improve the treatment of ischemia-relevant diseases.

Sign in / Sign up

Export Citation Format

Share Document