Parkinson disease

Nature Reviews Disease Primers, Год журнала: 2017, Номер 3(1)

Опубликована: Март 22, 2017

Язык: Английский

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Ageing as a risk factor for neurodegenerative disease

Nature Reviews Neurology, Год журнала: 2019, Номер 15(10), С. 565 - 581

Опубликована: Сен. 9, 2019

Язык: Английский

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Oxidative Stress: A Key Modulator in Neurodegenerative Diseases

Molecules, Год журнала: 2019, Номер 24(8), С. 1583 - 1583

Опубликована: Апрель 22, 2019

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

Язык: Английский

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Mechanisms of DNA damage, repair, and mutagenesis

Environmental and Molecular Mutagenesis, Год журнала: 2017, Номер 58(5), С. 235 - 263

Опубликована: Май 9, 2017

Living organisms are continuously exposed to a myriad of DNA damaging agents that can impact health and modulate disease-states. However, robust repair damage-bypass mechanisms faithfully protect the by either removing or tolerating damage ensure an overall survival. Deviations in this fine-tuning known destabilize cellular metabolic homeostasis, as exemplified diverse cancers where disruption deregulation pathways results genome instability. Because routinely used biological, physical chemical human health, testing their genotoxicity regulating use have become important. In introductory review, we will delineate counteracting repair/tolerance provide insights into molecular basis cells lays foundation for subsequent articles issue. Environ. Mol. Mutagen. 58:235-263, 2017. © 2017 Wiley Periodicals, Inc.

Язык: Английский

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Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

Chemical Reviews, Год журнала: 2017, Номер 117(15), С. 10043 - 10120

Опубликована: Июнь 27, 2017

Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, effective way to deliver drugs specifically mitochondria is by covalent linking a lipophilic cation such an alkyltriphenylphosphonium moiety pharmacophore interest. Other delocalized cations, rhodamine, natural synthetic mitochondria-targeting peptides, nanoparticle vehicles, have also been used mitochondrial delivery small molecules. Depending on approach used, cell membrane potentials, more than 1000-fold higher concentration can be achieved. Mitochondrial targeting has developed study physiology dysfunction interaction between other subcellular organelles treatment variety diseases neurodegeneration cancer. In this Review, we discuss efforts target small-molecule compounds probing function, diagnostic tools potential therapeutics. We describe physicochemical basis accumulation chemistry strategies mitochondria, probes, sensors, examples bioactive compounds. Finally, review published attempts apply mitochondria-targeted agents cancer neurodegenerative

Язык: Английский

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Mitochondrial electron transport chain, ROS generation and uncoupling (Review)

International Journal of Molecular Medicine, Год журнала: 2019, Номер unknown

Опубликована: Май 8, 2019

The mammalian mitochondrial electron transport chain (ETC) includes complexes I‑IV, as well the transporters ubiquinone and cytochrome c. There are two pathways in ETC: Complex I/III/IV, with NADH substrate complex II/III/IV, succinic acid substrate. flow is coupled generation of a proton gradient across inner membrane energy accumulated used by V (ATP synthase) to produce ATP. first part this review briefly introduces structure function I‑IV ATP synthase, including specific transfer process each complex. Some electrons directly transferred O2 generate reactive oxygen species (ROS) ETC. second discusses sites ROS ETC complex, IF IQ I, site IIF II IIIQo III, physiological pathological regulation ROS. As signaling molecules, play an important role cell proliferation, hypoxia adaptation fate determination, but excessive can cause irreversible damage even death. occurrence development number diseases closely related overproduction. Finally, leak uncoupling proteins (UCPS) discussed. Proton consists basal induced leak. Induced precisely regulated UCPs. A total five UCPs (UCP1‑5) have been identified cells. UCP1 mainly plays maintenance body temperature cold environment through non‑shivering thermogenesis. core UCP2‑5 reduce oxidative stress under certain conditions, therefore exerting cytoprotective effects. All involving associated

Язык: Английский

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Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

Frontiers in Pharmacology, Год журнала: 2018, Номер 9

Опубликована: Окт. 16, 2018

Aging is the progressive loss of organ and tissue function over time. Growing older positively linked to cognitive biological degeneration such as physical frailty, psychological impairment, decline. Oxidative stress considered an imbalance between pro- antioxidant species, which results in molecular cellular damage. plays a crucial role development age-related diseases. Emerging research evidence has suggested that can control autoxidation by interrupting propagation free radicals or inhibiting formation subsequently reduce oxidative stress, improve immune function, increase healthy longevity. Indeed, oxidation damage highly dependent on inherited acquired defects enzymes involved redox-mediated signaling pathways. Therefore, molecules with activity promote aging counteract worth discuss further. Of particular interest this article, we highlighted mechanisms antioxidants prevention Taken together, better understanding redox modulation inflammation would provide useful approach for potential interventions, promoting

Язык: Английский

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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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Role of ROS and Nutritional Antioxidants in Human Diseases

Frontiers in Physiology, Год журнала: 2018, Номер 9

Опубликована: Май 17, 2018

Overproduction of reactive oxygen species¬ (ROS) have been implicated in the development various chronic and degenerative diseases such as cancer, respiratory, neurodegenerative digestive diseases. Under physiological conditions, concentrations ROS are subtlety regulated by antioxidants, which can be either generated endogenously or externally supplemented. A combination antioxidant-deficiency malnutrition may render individuals more vulnerable to oxidative stress, increases risk cancer occurrence. In addition, antioxidant defense overwhelmed during sustained inflammation obstructive pulmonary diseases, inflammatory bowel disease, disorders. Certain vitamins, vitamin D, essential regulating biochemical pathways that lead proper functioning organs. Antioxidant supplementation has shown attenuate endogenous depletion thus alleviating associated damage some clinical research. However, results antioxidants exert no favorable effects on disease progression. Thus, studies warranted investigate complicated interactions between different types for restoration redox balance under pathologic conditions. This review highlights potential roles nutritional pathogenesis several imbalance-related attenuation stress-induced damages.

Язык: Английский

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Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications

Oxidative Medicine and Cellular Longevity, Год журнала: 2017, Номер 2017(1)

Опубликована: Янв. 1, 2017

Increasing numbers of individuals, particularly the elderly, suffer from neurodegenerative disorders. These diseases are normally characterized by progressive loss neuron cells and compromised motor or cognitive function. Previous studies have proposed that overproduction reactive oxygen species (ROS) may complex roles in promoting disease development. Research has shown vulnerable to oxidative damage due their high polyunsaturated fatty acid content membranes, consumption, weak antioxidant defense. However, exact molecular pathogenesis neurodegeneration related disturbance redox balance remains unclear. Novel antioxidants great potential mediating phenotypes could be an area interest for further research. In this review, we provide updated discussion on ROS pathological mechanisms Alzheimer’s disease, Huntington’s Parkinson’s amyotrophic lateral sclerosis, spinocerebellar ataxia, as well a highlight antioxidant‐based therapies alleviating severity.

Язык: Английский

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