scholarly journals Role of Oxidative Stress in the Pathogenesis of Amyotrophic Lateral Sclerosis: Antioxidant Metalloenzymes and Therapeutic Strategies

Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 437
Author(s):  
Pavlína Hemerková ◽  
Martin Vališ
Keyword(s):  
Oxidative Stress ◽  
Amyotrophic Lateral Sclerosis ◽  
Antioxidant Enzymes ◽  
Oxygen Radicals ◽  
Clinical Symptoms ◽  
Free Oxygen Radicals ◽  
Free Oxygen ◽  
Sporadic Als ◽  
Familial Form ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) affects motor neurons in the cerebral cortex, brainstem and spinal cord and leads to death due to respiratory failure within three to five years. Although the clinical symptoms of this disease were first described in 1869 and it is the most common motor neuron disease and the most common neurodegenerative disease in middle-aged individuals, the exact etiopathogenesis of ALS remains unclear and it remains incurable. However, free oxygen radicals (i.e., molecules containing one or more free electrons) are known to contribute to the pathogenesis of this disease as they very readily bind intracellular structures, leading to functional impairment. Antioxidant enzymes, which are often metalloenzymes, inactivate free oxygen radicals by converting them into a less harmful substance. One of the most important antioxidant enzymes is Cu2+Zn2+ superoxide dismutase (SOD1), which is mutated in 20% of cases of the familial form of ALS (fALS) and up to 7% of sporadic ALS (sALS) cases. In addition, the proper functioning of catalase and glutathione peroxidase (GPx) is essential for antioxidant protection. In this review article, we focus on the mechanisms through which these enzymes are involved in the antioxidant response to oxidative stress and thus the pathogenesis of ALS and their potential as therapeutic targets.

The Dinitrophenol and Potassium Iodate Influence on Hordeum Vulgare Seedlings Viability\

2018 ◽  
Vol 69 (8) ◽  
pp. 2160-2166
Author(s):  
Elena Todirascu Ciornea ◽  
Gabriela Dumitru ◽  
Ion Sandu
Keyword(s):  
Oxidative Stress ◽  
Hordeum Vulgare ◽  
Antioxidant Enzyme ◽  
Oxygen Radicals ◽  
Free Oxygen Radicals ◽  
Potassium Iodate ◽  
Free Oxygen ◽  
Oxidative Stress Enzymes ◽  
Stress Enzymes ◽  
Seeds Germination

The using of the pesticides of dinitrophenol type in agriculture has as consequence the major pollution of the environment, the plants taking these substances from the soil and once with these ones they reach in the human and animal organism where they product disequilibrium that are interpreted through the accumulation of free oxygen radicals with direct repercussions on the antioxidant enzyme�s synthesis intensification and on their activity�s increase. The apply of treatments on the barley seeds had significant effects regarding the seeds� germination, the young plants� growth, the oxidative stress enzymes� activity, but also regarding the content of photoassimilators and carotenoids pigments.

Markers of Neuroinflammation in the Serum of Prepubertal Children with Fetal Alcohol Spectrum Disorders

2021 ◽  
Vol 20 ◽  
Author(s):  
Marco Fiore ◽  
Carla Petrella ◽  
Giovanna Coriale ◽  
Pamela Rosso ◽  
Elena Fico ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxygen Radicals ◽  
Fetal Alcohol Spectrum Disorders ◽  
Serum Levels ◽  
Free Oxygen Radicals ◽  
Fetal Alcohol ◽  
Free Oxygen ◽  
Tnf Α ◽  
Spectrum Disorders ◽  
Fetal Alcohol Spectrum

Background: Fetal Alcohol Spectrum Disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with Fetal Alcohol Syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers. Alcohol drinking induces also oxidative stress. Hypothesis/Objective : The present study aims at investigating the potential association between neurotrophins, neuroinflammation and oxidative stress in 12 prepubertal male and female FASD children diagnosed as FAS or partial FAS (pFAS). Methods: Accordingly, we analyzed, in the serum, the level of BDNF and NGF and the oxidative stress, as free oxygen radicals test (FORT) and free oxygen radicals defense (FORD). Moreover, serum levels of inflammatory mediators (IL-1α, IL-2, IL-6, IL-10, IL-12, MCP-1, TGF-β and TNF-α) involved in neuroinflammatory and oxidative processes have been investigated. Results: We demonstrated in pre-pubertal FASD children low serum levels of NGF and BDNF, respect to healthy controls. These changes were associated with higher serum presence of TNF-α and IL-1α. Quite interestingly, an elevation in the FORD was also found despite normal FORT levels. Moreover, we found a potentiation of IL-1α, IL-2, IL-10 and IL-1α1 in the analyzed female compared to male children. Conclusion: The present investigation shows an imbalance in the peripheral neuroimmune pathways that could be used in children as early biomarkers of the deficits observed in FASD.

scholarly journals Pathological Roles of Wild-Type Cu, Zn-Superoxide Dismutase in Amyotrophic Lateral Sclerosis

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Yoshiaki Furukawa
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Motor Neurons ◽  
Wild Type ◽  
Sporadic Als ◽  
Familial Form ◽  
Recent Developments ◽  
Lateral Sclerosis

Dominant mutations in a Cu, Zn-superoxide dismutase (SOD1) gene cause a familial form of amyotrophic lateral sclerosis (ALS). While it remains controversial how SOD1 mutations lead to onset and progression of the disease, manyin vitroandin vivostudies have supported a gain-of-toxicity mechanism where pathogenic mutations contribute to destabilizing a native structure of SOD1 and thus facilitate misfolding and aggregation. Indeed, abnormal accumulation of SOD1-positive inclusions in spinal motor neurons is a pathological hallmark in SOD1-related familial ALS. Furthermore, similarities in clinical phenotypes and neuropathology of ALS cases with and without mutations insod1gene have implied a disease mechanism involving SOD1 common to all ALS cases. Although pathogenic roles of wild-type SOD1 in sporadic ALS remain controversial, recent developments of novel SOD1 antibodies have made it possible to characterize wild-type SOD1 under pathological conditions of ALS. Here, I have briefly reviewed recent progress on biochemical and immunohistochemical characterization of wild-type SOD1 in sporadic ALS cases and discussed possible involvement of wild-type SOD1 in a pathomechanism of ALS.

scholarly journals Pathophysiological Correlation between Cigarette Smoking and Amyotrophic Lateral Sclerosis

NeuroSci ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 120-134
Author(s):  
Spiro Menounos ◽  
Philip M. Hansbro ◽  
Ashish D. Diwan ◽  
Abhirup Das
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Risk Factor ◽  
Disease Process ◽  
Future Research ◽  
Environmental Risk Factor ◽  
Sporadic Als ◽  
Blood Spinal Cord Barrier ◽  
Lateral Sclerosis

Cigarette smoke (CS) has been consistently demonstrated to be an environmental risk factor for amyotrophic lateral sclerosis (ALS), although the molecular pathogenic mechanisms involved are yet to be elucidated. Here, we propose different mechanisms by which CS exposure can cause sporadic ALS pathogenesis. Oxidative stress and neuroinflammation are widely implicated in ALS pathogenesis, with blood–spinal cord barrier disruption also recognised to be involved in the disease process. In addition, immunometabolic, epigenetic and microbiome alterations have been implicated in ALS recently. Identification of the underlying pathophysiological mechanisms that underpin CS-associated ALS will drive future research to be conducted into new targets for treatment.

scholarly journals Reactive oxygen radicals – the therapeutic effectiveness of antioxidants

2016 ◽  
Vol 54 (1) ◽  
pp. 41-48
Author(s):  
Marta Skiba ◽  
Agnieszka Pedrycz ◽  
Beata Cichacz
Keyword(s):  
Oxidative Stress ◽  
Oxygen Radicals ◽  
Reactive Oxygen ◽  
Mitochondrial Respiratory Chain ◽  
Antioxidant Systems ◽  
Free Oxygen Radicals ◽  
Negative Effects ◽  
Free Oxygen ◽  
Cell Functions ◽  
Reactive Oxygen Forms

Abstract Oxidative stress occurring in cells is a consequence of an excessive activity of reactive oxygen forms, resulting from an imbalance between the release of free oxygen radicals and their removal from the cell by antioxidant systems. 90% of reactive oxygen radicals emerge in mitochondrial respiratory chain during an incomplete four-electron oxygen reduction. The remaining 10% originate from different reactions occurring in the cell. The established compounds are characterised by a short half-life and are highly reactive. Sparse quantities of free oxygen radicals have a positive effect on cell functions. Oxidative stress leads to damage in cellular membranes, enzymatic and non-enzymatic proteins, as well as DNA. Therapy with antioxidants as exogenous dietary supplements aims at preventing or reducing the risk of development of diseases involving the presence of the oxygen radicals. Whether the antioxidant therapy will bring positive or negative effects depends on numerous factors that need to be considered before their inclusion in the applied treatment.

scholarly journals SYSTEMIC OXIDATIVE STRESS AS A SURROGATE OF CORONARY ATHEROSCLEROTIC PLAQUE INSTABILITY AND RUPTURE PREDICTOR

2020 ◽  
Vol 6 (1) ◽  
pp. 26-34
Author(s):  
Z. Lominadze ◽  
K. Chelidze ◽  
L. Chelidze ◽  
E. Lominadze
Keyword(s):  
Oxidative Stress ◽  
Acute Coronary Syndrome ◽  
Atherosclerotic Plaque ◽  
Oxygen Radicals ◽  
Stress Profile ◽  
Free Oxygen Radicals ◽  
Free Oxygen ◽  
Plaque Instability ◽  
Coronary Syndrome ◽  
Life Threatening

Background. Oxidative stress is crucial in developing broad spectrum of diseases, including atherosclerosis and related life-threatening conditions, such as acute coronary syndrome (ACS) mainly caused by atherosclerotic plaque vulnerability. Objective. To clarify the relation between oxidative stress and plaque instability we decided to compare oxidative profiles of patients with acute coronary syndrome (ACS) and with chronic coronary syndrome (CCS), evaluated at admission to the coronary care unit (CCU) of LTD Clinic-LJ (Kutaisi, Georgia) in April 2018 - June 2019, who underwent successful primary percutaneous coronary intervention (PCI). Methods. 191 patients were enrolled (100 patients with ACS in Group 1 and 91 patients with CCS in Group 2) into the study. Using the CR3000 FORM PLUS (Callegari Srl, Catellani Group, Italy) – Callegari Point of Care instrument we evaluated free oxygen radical test (FORT), free oxygen radicals defense (FORD), calculated REDOX Index and the overall Profile of oxidative stress. Results. The mean/median concentration of Free Oxygen Radicals was significantly higher in the patients with ACS (404.37±9.83 Fort units/2.36 mmol/l H2O2 eq. vs 282.34±9.83 Fort units/2.36 mmol/l H2O2 eq., p<0.0001). Significant correlation was found between advanced oxidative stress and acute coronary syndrome (OR 14.42 95% CI (7.08-29.4), RR 3.26 95% CI (2.31-4.60) with high diagnostic characteristics (sensitivity of 82% and specificity of 92.3%; positive predictive value of 92% and positive likelihood ratio of 11). Conclusion. Oxidative stress is crucial in life-threatening acute coronary events. Measurement of overall oxidative stress profile, as a surrogate of plaque instability and rupture predictor, could help the clinicians in risk stratification and prevention of acute coronary syndrome (ACS).

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