Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging

Archives of Toxicology, Год журнала: 2023, Номер 97(10), С. 2499 - 2574

Опубликована: Авг. 19, 2023

Abstract A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or “good stress” characterized by low to mild levels oxidants involved in the regulation various biochemical transformations such carboxylation, hydroxylation, peroxidation, modulation signal transduction pathways Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2–related 2 (Nrf2) other processes. Increased ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result a harmful condition stress (“bad stress”). Although it widely accepted, that many chronic diseases are multifactorial origin, they share common denominator. Here we review importance mechanisms through which contributes pathological states an organism. Attention focused on chemistry ROS RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl nitric oxide, peroxynitrite), their role damage DNA, proteins, membrane lipids. Quantitative qualitative assessment biomarkers also discussed. Oxidative pathology cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer’s Parkinson’s Down syndrome), psychiatric (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, cancer), aging. The concerted action antioxidants ameliorate effect achieved antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), small molecular weight (vitamins C E, flavonoids, carotenoids, melatonin, ergothioneine, others). Perhaps one most effective vitamin first line defense against peroxidation promising approach appears be use flavonoids), showing weak prooxidant properties may boost cellular systems thus act preventive anticancer agents. Redox metal-based enzyme mimetic compounds potential pharmaceutical interventions sirtuins therapeutic targets for age-related anti-aging strategies

Язык: Английский

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Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease

Molecular Neurodegeneration, Год журнала: 2020, Номер 15(1)

Опубликована: Июль 16, 2020

Abstract Alzheimer’s disease (AD) is the most common neurodegenerative disorder seen in age-dependent dementia. There currently no effective treatment for AD, which may be attributed part to lack of a clear underlying mechanism. Studies within last few decades provide growing evidence central role amyloid β (Aβ) and tau, as well glial contributions various molecular cellular pathways AD pathogenesis. Herein, we review recent progress with respect Aβ- tau-associated mechanisms, discuss dysfunction emphasis on neuronal receptors that mediate Aβ-induced toxicity. We also other critical factors affect pathogenesis, including genetics, aging, variables related environment, lifestyle habits, describe potential apolipoprotein E (APOE), viral bacterial infection, sleep, microbiota. Although have gained much towards understanding aspects this devastating disorder, greater commitment research mechanism, diagnostics will needed future research.

Язык: Английский

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Essential metals in health and disease

Chemico-Biological Interactions, Год журнала: 2022, Номер 367, С. 110173 - 110173

Опубликована: Сен. 22, 2022

In total, twenty elements appear to be essential for the correct functioning of human body, half which are metals and non-metals. Among those that currently considered normal biological four main group elements, sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), six d-block transition metal manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn) molybdenum (Mo). Cells have developed various metallo-regulatory mechanisms maintaining a necessary homeostasis metal-ions diverse cellular processes, most importantly in central nervous system. Since redox active (for example Fe Cu) may participate electron transfer reactions, their must carefully controlled. The catalytic behaviour escaped control, e.g. via Fenton reaction, results formation reactive hydroxyl radicals, cause damage DNA, proteins membranes. Transition integral parts centers numerous enzymes (e.g. Cu,Zn-SOD, Mn-SOD, Catalase) catalyze chemical reactions at physiologically compatible rates. Either deficiency, or an excess result disease states arising organism. Some typical ailments characterized by disturbed include neurological disorders (Alzheimer's, Parkinson's Huntington's disorders), mental health problems, cardiovascular diseases, cancer, diabetes. To comprehend more deeply metals, acting either alone combination, and/or through interaction with non-essential chromium) function systems will require application broader, interdisciplinary approach than has mainly been used so far. It is clear stronger cooperation between bioinorganic chemists biophysicists - who already achieved great success understanding structure role metalloenzymes living biologists, access new avenues research biology ions. With this mind, present paper reviews selected aspects ions possible interactions under pathological conditions.

Язык: Английский

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An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(11), С. 5938 - 5938

Опубликована: Май 25, 2022

Oxidative stress has been linked with a variety of diseases, being involved in the debut and/or progress several neurodegenerative disorders. This review intends to summarize some findings that correlate overproduction reactive oxygen species pathophysiology Alzheimer’s disease, Parkinson’s Huntington’s and amyotrophic lateral sclerosis. was also noted modify inflammatory response. Even though oxidative neuroinflammation are two totally different pathological events, they affect one another. Nonetheless, there still mechanisms need be understood regarding onset diseases order develop efficient therapies. As antioxidants means alter slow down symptoms these most common antioxidants, enzymatic as well non-enzymatic, have mentioned this paper therapeutic options for discussed

Язык: Английский

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The molecular mechanisms of copper metabolism and its roles in human diseases

Pflügers Archiv - European Journal of Physiology, Год журнала: 2020, Номер 472(10), С. 1415 - 1429

Опубликована: Июнь 7, 2020

Язык: Английский

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Myricetin: A review of the most recent research

Biomedicine & Pharmacotherapy, Год журнала: 2020, Номер 134, С. 111017 - 111017

Опубликована: Дек. 17, 2020

Myricetin(MYR) is a flavonoid compound widely found in many natural plants including bayberry. So far, MYR has been proven to have multiple biological functions and it with promising research development prospects. This review comprehensively retrieved collected the latest pharmacological abstracts on MYR, discussed potential molecular mechanisms of its effects. The results our indicated that therapeutic effect diseases, tumors different types, inflammatory atherosclerosis, thrombosis, cerebral ischemia, diabetes, Alzheimer's disease pathogenic microbial infections. Furthermore, regulates expression Hippo, MAPK, GSK-3β, PI3K/AKT/mTOR, STAT3, TLR, IκB/NF-κB, Nrf2/HO-1, ACE, eNOS / NO, AChE BrdU/NeuN. also enhances immunomodulatory functions, suppresses cytokine storms, improves cardiac dysfunction, possesses an antiviral potential, can be used as adjuvant treatment against cancer, cardiovascular injury nervous system may drug COVID-19 other viral Generally, this article provides theoretical basis for clinical application reference further use.

Язык: Английский

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Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants

Archives of Toxicology, Год журнала: 2024, Номер 98(5), С. 1323 - 1367

Опубликована: Март 14, 2024

Abstract Reactive oxygen species (ROS) and reactive nitrogen (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production elimination is termed oxidative stress, critical factor common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic neurological disorders (Alzheimer’s Parkinson’s diseases), other disorders. To counteract the harmful effects ROS, organisms have evolved complex, three-line antioxidant defense system. The first-line mechanism most efficient involves enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx). This line plays an irreplaceable role in dismutation radicals (O 2 ·− ) hydrogen peroxide (H O ). removal by SOD prevents formation much more damaging peroxynitrite ONOO − + NO · → maintains physiologically relevant level nitric oxide (NO ), important molecule neurotransmission, inflammation, vasodilation. second-line pathway exogenous diet-derived small-molecule antioxidants. third-line ensured repair oxidized proteins biomolecules variety enzyme review briefly discusses endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) (e.g., smoking, radiation, drugs, pollution) sources (superoxide radical, peroxide, hydroxyl peroxyl hypochlorous acid, peroxynitrite). Attention has been given system provided SOD, CAT, GPx. chemical molecular mechanisms enzymes, enzyme-related (cancer, cardiovascular, lung, metabolic, GPx4) cellular processes ferroptosis discussed. Potential therapeutic applications mimics recent progress metal-based (copper, iron, cobalt, molybdenum, cerium) nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) also Moreover, attention action low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids β-carotene, lycopene, lutein), flavonoids quercetin, anthocyanins, epicatechin), (GSH)), activation transcription factors Nrf2, protection against diseases. Given that there discrepancy preclinical clinical studies, approaches may result greater pharmacological success therapies subject discussion.

Язык: Английский

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Oxidative stress in alzheimer’s disease: A review on emergent natural polyphenolic therapeutics

Complementary Therapies in Medicine, Год журнала: 2019, Номер 49, С. 102294 - 102294

Опубликована: Дек. 31, 2019

Язык: Английский

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Amyloid Beta in Aging and Alzheimer’s Disease

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(21), С. 12924 - 12924

Опубликована: Окт. 26, 2022

Alzheimer’s disease (AD), is a progressive neurodegenerative that affects behavior, thinking, learning, and memory in elderly individuals. AD occurs two forms, early onset familial late-onset sporadic; genetic mutations PS1, PS2, APP genes cause AD, combination of lifestyle, environment factors causes the sporadic form disease. However, accelerated progression noticed patients with AD. Disease-causing pathological changes are synaptic damage, mitochondrial structural functional changes, addition to increased production accumulation phosphorylated tau (p-tau), amyloid beta (Aβ) affected brain regions patients. Aβ peptide derived from precursor protein (APP) by proteolytic cleavage gamma secretases. glycoprotein plays significant role maintaining neuronal homeostasis like signaling, development, intracellular transport. reported have both protective toxic effects neurons. The purpose our article summarize recent developments its association synapses, mitochondria, microglia, astrocytes, interaction p-tau. Our also covers therapeutic strategies reduce toxicities discusses reasons for failures therapeutics.

Язык: Английский

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Recent advances in Alzheimer’s disease: Mechanisms, clinical trials and new drug development strategies

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 23, 2024

Abstract Alzheimer’s disease (AD) stands as the predominant form of dementia, presenting significant and escalating global challenges. Its etiology is intricate diverse, stemming from a combination factors such aging, genetics, environment. Our current understanding AD pathologies involves various hypotheses, cholinergic, amyloid, tau protein, inflammatory, oxidative stress, metal ion, glutamate excitotoxicity, microbiota-gut-brain axis, abnormal autophagy. Nonetheless, unraveling interplay among these pathological aspects pinpointing primary initiators require further elucidation validation. In past decades, most clinical drugs have been discontinued due to limited effectiveness or adverse effects. Presently, available primarily offer symptomatic relief often accompanied by undesirable side However, recent approvals aducanumab ( 1 ) lecanemab 2 Food Drug Administration (FDA) present potential in disrease-modifying Nevertheless, long-term efficacy safety need Consequently, quest for safer more effective persists formidable pressing task. This review discusses pathogenesis, advances diagnostic biomarkers, latest updates trials, emerging technologies drug development. We highlight progress discovery selective inhibitors, dual-target allosteric modulators, covalent proteolysis-targeting chimeras (PROTACs), protein-protein interaction (PPI) modulators. goal provide insights into prospective development application novel drugs.

Язык: Английский

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