Biochemical integrity of the brain is vital for normal functioning of the central nervous system (CNS). One of the factors contributing to cerebral biochemical impairment is a chemical process called oxidative stress. Oxidative stress occurs upon excessive free radical production resulting from an insufficiency of the counteracting antioxidant response system. The brain, with its high oxygen consumption and lipid-rich content, is highly susceptible to oxidative stress. Therefore, oxidative stress–induced damage to the brain has a strong potential to negatively impact normal CNS functions. Although oxidative stress has historically been considered to be involved mainly in neurodegenerative disorders such as Alzheimer disease, Huntington disease, and Parkinson disease, its involvement in neuropsychiatric disorders, including anxiety disorders and depression, is beginning to be recognized. This review is a discussion of the relevance of cerebral oxidative stress to impairment of emotional and mental well-being.

https://jpet.aspetjournals.org/content/jpet/360/1/201.full.pdf

Oxidative Stress and the Central Nervous System.

Oxidative stress plays an essential role in the pathogenesis of chronic diseases such as cardiovascular diseases, diabetes, neurodegenerative diseases, and cancer. Long term exposure to increased levels of pro-oxidant factors can cause structural defects at a mitochondrial DNA level, as well as functional alteration of several enzymes and cellular structures leading to aberrations in gene expression. The modern lifestyle associated with processed food, exposure to a wide range of chemicals and lack of exercise plays an important role in oxidative stress induction. However, the use of medicinal plants with antioxidant properties has been exploited for their ability to treat or prevent several human pathologies in which oxidative stress seems to be one of the causes. In this review we discuss the diseases in which oxidative stress is one of the triggers and the plant-derived antioxidant compounds with their mechanisms of antioxidant defenses that can help in the prevention of these diseases. Finally, both the beneficial and detrimental effects of antioxidant molecules that are used to reduce oxidative stress in several human conditions are discussed.

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Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases.

Semiconducting polymer nanoparticles are used to image toxic reactive oxygen and reactive nitrogen species in live mice.

/pdf/real-time-imaging-of-oxidative-and-nitrosative-stress-in-the-391hldg7v1.pdf

Real-time imaging of oxidative and nitrosative stress in the liver of live animals for drug-toxicity testing

The pathophysiologies of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD), are far from being fully explained. Oxidative stress (OS) has been proposed as one factor that plays a potential role in the pathogenesis of neurodegenerative disorders. Clinical and preclinical studies indicate that neurodegenerative diseases are characterized by higher levels of OS biomarkers and by lower levels of antioxidant defense biomarkers in the brain and peripheral tissues. In this article, we review the current knowledge regarding the involvement of OS in neurodegenerative diseases, based on clinical trials and animal studies. In addition, we analyze the effects of the drug-induced modulation of oxidative balance, and we explore pharmacotherapeutic strategies for OS reduction.

/pdf/oxidative-stress-in-neurodegenerative-diseases-4msd3rys8x.pdf

Oxidative Stress in Neurodegenerative Diseases

Significance: Alzheimer disease (AD) is an age-related neurodegenerative disease. AD is characterized by progressive cognitive impairment. One of the main histopathological hallmarks of AD brain is the presence of senile plaques (SPs) and another is elevated oxidative stress. The main component of SPs is amyloid beta-peptide (Aβ) that is derived from the proteolytic cleavage of amyloid precursor protein. Recent Advances: Recent studies are consistent with the notion that methionine present at 35 position of Aβ is critical to Aβ-induced oxidative stress and neurotoxicity. Further, we also discuss the signatures of oxidatively modified brain proteins, identified using redox proteomics approaches, during the progression of AD. Critical Issues: The exact relationships of the specifically oxidatively modified proteins in AD pathogenesis require additional investigation. Future Directions: Further studies are needed to address whether the therapies directed toward brain oxidative stress and oxidatively...

https://chem.as.uky.edu/sites/default/files/Butterfield%20et%20al%202013%20Antioxidant%20and%20Redox%20Signal%2019%20823-835.pdf

Amyloid β-Peptide (1–42)-Induced Oxidative Stress in Alzheimer Disease: Importance in Disease Pathogenesis and Progression

Living cells continually generate reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS at low or moderate concentration can play important physiological roles. However, an excessive amount of ROS under oxidative stress would be extremely deleterious. The central nervous system (CNS) is particularly vulnerable to oxidative stress due to its high oxygen consumption, weakly antioxidative systems and the terminal-differentiation characteristic of neurons. Thus, oxidative stress elicits various neurodegenerative diseases. In addition, chemotherapy could result in severe side effects on the CNS and peripheral nervous system (PNS) of cancer patients, and a growing body of evidence demonstrates the involvement of ROS in drug-induced neurotoxicities as well. Therefore, development of antioxidants as neuroprotective drugs is a potentially beneficial strategy for clinical therapy. In this review, we summarize the source, balance maintenance and physiologic functions of ROS, oxidative stress and its toxic mechanisms underlying a number of neurodegenerative diseases, and the possible involvement of ROS in chemotherapy-induced toxicity to the CNS and PNS. We ultimately assess the value for antioxidants as neuroprotective drugs and provide our comments on the unmet needs.

https://www.mdpi.com/1422-0067/14/12/24438/pdf

Wei Li

Papers

Oxidative Stress and Neurodegenerative Disorders