Interrelation of Oxidative Stress and Inflammation in Neurodegenerative Disease: Role of TNF

Oxidative Medicine and Cellular Longevity, Journal Year: 2015, Volume and Issue: 2015, P. 1 - 18

Published: Jan. 1, 2015

Neuroinflammation and mitochondrial dysfunction are common features of chronic neurodegenerative diseases the central nervous system. Both conditions can lead to increased oxidative stress by excessive release harmful reactive oxygen nitrogen species (ROS RNS), which further promote neuronal damage subsequent inflammation resulting in a feed-forward loop neurodegeneration. The cytokine tumor necrosis factor (TNF), master regulator immune system, plays an important role propagation due activation recruitment cells via its receptor TNF 1 (TNFR1). Moreover, TNFR1 directly induce ROS RNS producing enzymes. TNF-induced interact cooperate However, dual disease, since stimulation second receptor, TNFR2, is neuroprotective promotes tissue regeneration. Here we review interrelation two major diseases, Alzheimer's Parkinson's discuss promoting neurodegeneration regeneration receptors.

Language: Английский

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Oxidative stress in the aging substantia nigra and the etiology of Parkinson's disease

Aging Cell, Journal Year: 2019, Volume and Issue: 18(6)

Published: Aug. 20, 2019

Abstract Parkinson's disease prevalence is rapidly increasing in an aging global population. With this increase comes exponentially rising social and economic costs, emphasizing the immediate need for effective disease‐modifying treatments. Motor dysfunction results from loss of dopaminergic neurons substantia nigra pars compacta depletion dopamine nigrostriatal pathway. While a specific biochemical mechanism remains elusive, oxidative stress plays undeniable role complex progressive neurodegenerative cascade. This review will explore molecular factors that contribute to high steady‐state healthy during aging, how chemical environment renders susceptible damage disease. Contributing as pathogenic be discussed within context why therapeutic approaches targeting cellular redox activity disorder have, date, yielded little benefit. We present contemporary perspective on central contribution imbalance etiology argue improving our ability accurately measure stress, neurotransmission cell death pathways vivo crucial both development new therapies identification novel biomarkers.

Language: Английский

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Oxidative stress: A major pathogenesis and potential therapeutic target of antioxidative agents in Parkinson’s disease and Alzheimer’s disease

Progress in Neurobiology, Journal Year: 2016, Volume and Issue: 147, P. 1 - 19

Published: Oct. 19, 2016

Language: Английский

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Development of Multifunctional Molecules as Potential Therapeutic Candidates for Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis in the Last Decade

Chemical Reviews, Journal Year: 2018, Volume and Issue: 119(2), P. 1221 - 1322

Published: Aug. 10, 2018

Neurodegenerative diseases pose a substantial socioeconomic burden on society. Unfortunately, the aging world population and lack of effective cures foreshadow negative outlook. Although large amount research has been dedicated to elucidating pathologies neurodegenerative diseases, their principal causes remain elusive. Metal ion dyshomeostasis, proteopathy, oxidative stress, neurotransmitter deficiencies are pathological features shared across multiple disorders. In addition, these factors proposed be interrelated upon disease progression. Thus, development multifunctional compounds capable simultaneously interacting with several components suggested as solution undertake complex diseases. this review, we outline discuss possible therapeutic targets in Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis molecules, previously designed or discovered potential drug candidates for disorders emphasis multifunctionality. underrepresented areas discussed indicate new directions.

Language: Английский

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Parkinson's disease: Mechanisms, translational models and management strategies

Life Sciences, Journal Year: 2019, Volume and Issue: 226, P. 77 - 90

Published: April 10, 2019

Language: Английский

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NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology

Antioxidants, Journal Year: 2021, Volume and Issue: 10(6), P. 890 - 890

Published: June 1, 2021

The reactive oxygen species (ROS)-producing enzyme NADPH oxidase (NOX) was first identified in the membrane of phagocytic cells. For many years, its only known role immune defense, where ROS production leads to destruction pathogens by NOX from phagocytes catalyzes, via one-electron trans-membrane transfer molecular oxygen, superoxide anion. Over six human homologs catalytic subunit phagocyte were found: NOX1, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Together with NOX2/gp91phox component present assembly itself, are now referred as family oxidases. complex multidomain proteins varying requirements for combinations other activity. recent structural insights acquired on both prokaryotic eukaryotic open new perspectives understanding mechanisms inherent regulation (superoxide or hydrogen peroxide). This information will certainly inform investigations disease. As specialized producers, enzymes participate numerous crucial physiological processes, including host post-translational processing proteins, cellular signaling, gene expression, cell differentiation. These diversities context be discussed this review. We also discuss misregulation, which can contribute a wide range severe pathologies, such atherosclerosis, hypertension, diabetic nephropathy, lung fibrosis, cancer, neurodegenerative diseases, giving strong therapeutic interest.

Language: Английский

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The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease: A Mini Review

Oxidative Medicine and Cellular Longevity, Journal Year: 2016, Volume and Issue: 2016(1)

Published: Jan. 1, 2016

Neurodegenerative diseases affect not only the life quality of aging populations, but also their spans. All forms neurodegenerative have a massive impact on elderly. The major threat these brain includes progressive loss memory, Alzheimer's disease (AD), impairments in movement, Parkinson's (PD), and inability to walk, talk, think, Huntington's (HD). Oxidative stress mitochondrial dysfunction are highlighted as central feature degenerative diseases. stress, condition that occurs due imbalance oxidant antioxidant status, has been known play vital role pathophysiology including AD, PD, HD. A large number studies utilized oxidative biomarkers investigate severity medications available, treat symptoms. In traditional medicine, medicinal plants used symptoms Extensive scientifically validated beneficial effect natural products against using suitable animal models. This short review focuses pathogenesis HD protective efficacy

Language: Английский

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Current understanding of the molecular mechanisms in Parkinson's disease: Targets for potential treatments

Translational Neurodegeneration, Journal Year: 2017, Volume and Issue: 6(1)

Published: Oct. 23, 2017

Gradual degeneration and loss of dopaminergic neurons in the substantia nigra, pars compacta subsequent reduction dopamine levels striatum are associated with motor deficits that characterize Parkinson's disease (PD). In addition, half PD patients also exhibit frontostriatal-mediated executive dysfunction, including attention, short-term working memory, speed mental processing, impulsivity. The most commonly used treatments for only partially or transiently effective available applicable to a minority patients. Because, these therapies neither restore lost degenerated neurons, nor prevent delay progression, need more therapeutics is critical. this review, we provide comprehensive overview current understanding molecular signaling pathways involved PD, particularly within context how genetic environmental factors contribute initiation progression disease. involvement chaperones, autophagy-lysosomal pathways, proteasome systems highlighted. emerging therapies, pharmacological manipulations, surgical procedures, stem cell transplantation, gene therapy, as well complementary, supportive rehabilitation complex reviewed.

Language: Английский

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Rutin as a Potent Antioxidant: Implications for Neurodegenerative Disorders

Oxidative Medicine and Cellular Longevity, Journal Year: 2018, Volume and Issue: 2018(1)

Published: Jan. 1, 2018

A wide range of neurodegenerative diseases (NDs), including Alzheimer’s disease, Parkinson’s Huntington’s and prion diseases, share common mechanisms such as neuronal loss, apoptosis, mitochondrial dysfunction, oxidative stress, inflammation. Intervention strategies using plant‐derived bioactive compounds have been offered a form treatment for these debilitating conditions, there are currently no remedies to prevent, reverse, or halt the progression loss. Rutin, glycoside flavonoid quercetin, is found in many plants fruits, especially buckwheat, apricots, cherries, grapes, grapefruit, plums, oranges. Pharmacological studies reported beneficial effects rutin disease its therapeutic potential several models NDs has created considerable excitement. Here, we summarized current knowledge on neuroprotective various experimental NDs. The action reviewed this article include reduction proinflammatory cytokines, improved antioxidant enzyme activities, activation mitogen‐activated protein kinase cascade, downregulation mRNA expression PD‐linked proapoptotic genes, upregulation ion transport antiapoptotic restoration activities complex enzymes. Taken together, findings suggest that may be promising compound

Language: Английский

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Role of TLR4 in the gut-brain axis in Parkinson’s disease: a translational study from men to mice

Gut, Journal Year: 2018, Volume and Issue: 68(5), P. 829 - 843

Published: Dec. 15, 2018

Objective Recent evidence suggesting an important role of gut-derived inflammation in brain disorders has opened up new directions to explore the possible gut-brain axis neurodegenerative diseases. Given prominence dysbiosis and colonic dysfunction patients with Parkinson’s disease (PD), we propose that toll-like receptor 4 (TLR4)-mediated intestinal could contribute central PD-related neurodegeneration. Design To test this hypothesis performed studies both human tissue a murine model PD. Inflammation, immune activation microbiota composition were measured samples from subjects PD healthy controls rotenone or vehicle-treated mice. further assess TLR4 signalling PD-induced neuroinflammation, used TLR4-knockout (KO) mice conjunction oral administration Results Patients have barrier disruption, enhanced markers microbial translocation higher pro-inflammatory gene profiles biopsy compared controls. In regard, found increased expression bacterial endotoxin-specific ligand TLR4, CD3+ T cells, cytokine biopsies, characterised by decrease abundance SCFA-producing bacteria Rotenone treatment TLR4-KO revealed less inflammation, motor dysfunction, neuroinflammation neurodegeneration, relative rotenone-treated wild-type animals despite presence dysbiotic Conclusion Taken together, these suggest TLR4-mediated plays and/or which may be one key factors leading neurodegeneration

Language: Английский

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