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

Frontiers in Pharmacology, Journal Year: 2018, Volume and Issue: 9

Published: Oct. 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

Language: Английский

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Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2017, Volume and Issue: 88(10), P. 876 - 882

Published: Aug. 9, 2017

Objectives

Increasing evidence suggests that inflammation is involved in Alzheimer’s disease (AD) pathology. This study quantitatively summarised the data on peripheral inflammatory markers patients with AD compared healthy controls (HC).

Methods

Original reports containing measurements of and HC were included for meta-analysis. Standardised mean differences calculated using a random effects model. Meta-regression exploration heterogeneity was performed publication year, age, gender, Mini-Mental State Examination (MMSE) scores, plasma versus serum immunoassay type.

Results

A total 175 studies combined to review 51 analytes 13 344 12 912 patients. Elevated interleukin (IL)-1β, IL-2, IL-6, IL-18, interferon-γ, homocysteine, high-sensitivity C reactive protein, C-X-C motif chemokine-10, epidermal growth factor, vascular cell adhesion molecule-1, tumour necrosis factor (TNF)-α converting enzyme, soluble TNF receptors 1 2, α1-antichymotrypsin decreased IL-1 receptor antagonist leptin found HC. IL-6 levels inversely correlated MMSE scores.

Conclusions

These findings suggest accompanied by response may be useful biological marker correlate severity cognitive impairment. Further are needed determine clinical utility these markers.

Language: Английский

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Autophagy and Alzheimer’s Disease: From Molecular Mechanisms to Therapeutic Implications

Frontiers in Aging Neuroscience, Journal Year: 2018, Volume and Issue: 10

Published: Jan. 30, 2018

Alzheimer's disease (AD) is the most common cause of progressive dementia in elderly. It characterized by a and irreversible loss cognitive abilities formation senile plaques, composed mainly amyloid β (Aβ), neurofibrillary tangles (NFTs), tau protein, hippocampus cortex afflicted humans. In brains AD patients metabolism Aβ dysregulated, which leads to accumulation aggregation Aβ. Metabolism proteins crucially influenced autophagy. Autophagy lysosome-dependent, homeostatic process, organelles are degraded recycled into energy. Thus, dysfunction autophagy suggested lead accretion noxious brain. present review, we describe process its importance AD. Additionally, discuss mechanisms genes linking AD, i.e., mTOR pathway, neuroinflammation, endocannabinoid system, ATG7, BCL2, BECN1, CDK5, CLU, CTSD, FOXO1, GFAP, ITPR1, MAPT, PSEN1, SNCA, UBQLN1, UCHL1. We also pharmacological agents acting via modulation that may show promise therapy. This review updates our knowledge on proposing novel therapeutic targets for treatment

Language: Английский

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Alzheimer’s disease and its treatment by different approaches: A review

European Journal of Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 216, P. 113320 - 113320

Published: Feb. 23, 2021

Language: Английский

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Damage to dopaminergic neurons by oxidative stress in Parkinson's disease (Review)

International Journal of Molecular Medicine, Journal Year: 2018, Volume and Issue: unknown

Published: Jan. 19, 2018

Oxidative stress is increasingly recognized as a central event contributing to the degeneration of dopaminergic neurons in pathogenesis Parkinson's disease (PD). Although reactive oxygen species (ROS) production implicated causative factor PD, cellular and molecular mechanisms linking oxidative with neuron death are complex not well characterized. The primary insults cause greatest ROS, which contributes damage by attacking all macromolecules, including lipids, proteins nucleic acids, leading defects their physiological function. Consequently, these macromolecules result mitochondrial dysfunction neuroinflammation, subsequently enhance ROS ultimately neuronal damage. interaction between various forms positive feedback loop that drives progressive loss stress‑mediated appears serve role neurodegenerative process. Thus, understanding may provide promising therapeutic approach PD treatment.

Language: Английский

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Role of inflammatory molecules in the Alzheimer's disease progression and diagnosis

Journal of the Neurological Sciences, Journal Year: 2017, Volume and Issue: 376, P. 242 - 254

Published: March 22, 2017

Language: Английский

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Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2015, Volume and Issue: 48(2), P. 319 - 353

Published: Sept. 9, 2015

This review focuses on research in epidemiology, neuropathology, molecular biology, and genetics regarding the hypothesis that pathogens interact with susceptibility genes are causative sporadic Alzheimer's disease (AD).Sporadic AD is a complex multifactorial neurodegenerative evidence indicating coexisting multi-pathogen inflammatory etiologies.There significant associations between various pathogens, including Herpes simplex virus type 1 (HSV-1), Cytomegalovirus, other Herpesviridae, Chlamydophila pneumoniae, spirochetes, Helicobacter pylori, periodontal pathogens.These able to evade destruction by host immune system, leading persistent infection.Bacterial viral DNA RNA bacterial ligands increase expression of pro-inflammatory molecules activate innate adaptive systems.Evidence demonstrates directly indirectly induce pathology, amyloid-␤ (A␤) accumulation, phosphorylation tau protein, neuronal injury, apoptosis.Chronic brain infection HSV-1, spirochetes results processes cause vicious cycle uncontrolled neuroinflammation neurodegeneration.Infections such as production systemic cytokines may cross blood-brain barrier promote neurodegeneration.Pathogen-induced inflammation central nervous system accumulation A␤ damages barrier, which contributes pathophysiology AD.Apolipoprotein E4 (ApoE4) enhances infiltration HSV-1 pneumoniae.ApoE4 also associated an increased response system.Potential antimicrobial treatments for discussed, rationale antiviral antibiotic clinical trials.

Language: Английский

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Treadmill Exercise Exerts Neuroprotection and Regulates Microglial Polarization and Oxidative Stress in a Streptozotocin-Induced Rat Model of Sporadic Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2017, Volume and Issue: 56(4), P. 1469 - 1484

Published: Feb. 1, 2017

Recent work has suggested that exercise may be beneficial in preventing or ameliorating symptoms of several neurological disorders, although the mechanism is not entirely understood. The current study was designed to examine potential effect treadmill upon cognitive function a streptozotocin (STZ)-induced rat model Alzheimer’s disease (AD). Animals underwent (30 min/day, 5 days/week) for 4 weeks after bilateral STZ intracerebroventricular injection (2.4 mg/kg). We demonstrated significantly attenuated STZ-induced neurodegeneration hippocampal CA1 region and strongly preserved hippocampal-dependent functioning. Further mechanistic investigation displayed marked suppression amyloid-β accumulation tau phosphorylation. Intriguingly, remarkably inhibited reactive gliosis following insult effectively shifted activated microglia from pro-inflammatory M1 an anti-inflammatory M2 phenotype, which correlated with reduced expression mediators corresponding enhancement cytokine hippocampus. Furthermore, caused robust oxidative damage as evidenced by peroxynitrite production, lipid peroxidation, oxidized DNA damage. Finally, mitochondrial dysfunction manifested dramatically elevated intra-mitochondrial cytochrome c oxidase activity ATP synthesis, markedly neuronal apoptosis These findings demonstrate multifactorial attenuate many pathological processes play key role AD, provide further support therapeutic option AD treatment.

Language: Английский

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ER stress and UPR in Alzheimer’s disease: mechanisms, pathogenesis, treatments

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(8)

Published: Aug. 15, 2022

Abstract Alzheimer’s disease (AD) is a devastating neurodegenerative disorder characterized by gradual loss of memory and cognitive function, which constitutes heavy burden on the healthcare system globally. Current therapeutics to interfere with underlying process in AD still under development. Although many efforts have centered toxic forms Aβ effectively tackle AD, considering unsatisfactory results so far it vital examine other targets therapeutic approaches as well. The endoplasmic reticulum (ER) stress refers build-up unfolded or misfolded proteins within ER, thus, perturbing ER cellular homeostasis. Emerging evidence indicates that contributes onset development AD. A thorough elucidation machinery pathology may help open up new avenues management this condition relieve dementia symptoms. Herein, we aim at deciphering unique role pathogenesis, reviewing key findings, existing controversy an attempt summarize plausible interventions pathophysiology.

Language: Английский

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The amyloid cascade hypothesis: an updated critical review

Brain, Journal Year: 2023, Volume and Issue: 146(10), P. 3969 - 3990

Published: May 15, 2023

Results from recent clinical trials of antibodies that target amyloid-β (Aβ) for Alzheimer's disease have created excitement and been heralded as corroboration the amyloid cascade hypothesis. However, while Aβ may contribute to disease, genetic, clinical, imaging biochemical data suggest a more complex aetiology. Here we review history weaknesses hypothesis in view new evidence obtained anti-amyloid antibodies. These indicate treatments either no or uncertain effect on cognition. Despite importance definition argue point playing minor aetiological role. We also discuss suggesting concerted activity many pathogenic factors propose evolving multi-factor models will better underpin search effective strategies treat disease.

Language: Английский

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