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      Role of oxidative stress in neurodegenerative disorders: a review of reactive oxygen species and prevention by antioxidants

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          Abstract

          Neurological disorders include a variety of conditions, including Alzheimer’s disease, motor neuron disease and Parkinson’s disease, affecting longevity and quality of life, and their pathogenesis is associated with oxidative stress. Several of the chronic neurodegenerative pathologies of the CNS share some common features, such as oxidative stress, inflammation, synapse dysfunctions, protein misfolding and defective autophagia. Neuroinflammation can involve the activation of mast cells, contributing to oxidative stress, in addition to other sources of reactive oxygen species. Antioxidants can powerfully neutralize reactive oxygen species and free radicals, decreasing oxidative damage. Antioxidant genes, like the manganese superoxide dismutase enzyme, can undergo epigenetic changes that reduce their expression, thus increasing oxidative stress in tissue. Alternatively, DNA can be altered by free radical damage. The epigenetic landscape of these genes can change antioxidant function and may result in neurodegenerative disease. This imbalance of free radical production and antioxidant function increases the reactive oxygen species that cause cell damage in neurons and is often observed as an age-related event. Increased antioxidant expression in mice is protective against reactive oxygen species in neurons as is the exogenous supplementation of antioxidants. Manganese superoxide dismutase requires manganese for its enzymic function. Antioxidant therapy is considered for age-related neurodegenerative diseases, and a new mimetic of a manganese superoxide dismutase, avasopasem manganese, is described and suggested as a putative treatment to reduce the oxidative stress that causes neurodegenerative disease. The aim of this narrative review is to explore the evidence that oxidative stress causes neurodegenerative damage and the role of antioxidant genes in inhibiting reactive oxygen species damage. Can the neuronal environment of oxidative stress, causing neuroinflammation and neurodegeneration, be reduced or reversed?

          Abstract

          Neurological disorders, including Alzheimer’s disease, affect longevity and quality of life. Neurodegenerative pathologies share common features, like oxidative stress, closely related to inflammation, synapse dysfunctions, protein misfolding and defective autophagia. Antioxidant enzymes, like the manganese superoxide dismutase, can powerfully neutralize reactive oxygen species, decreasing neurological oxidative damage and inflammatory mechanisms.

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          Most cited references81

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          ROS function in redox signaling and oxidative stress.

          Oxidative stress refers to elevated intracellular levels of reactive oxygen species (ROS) that cause damage to lipids, proteins and DNA. Oxidative stress has been linked to a myriad of pathologies. However, elevated ROS also act as signaling molecules in the maintenance of physiological functions--a process termed redox biology. In this review we discuss the two faces of ROS--redox biology and oxidative stress--and their contribution to both physiological and pathological conditions. Redox biology involves a small increase in ROS levels that activates signaling pathways to initiate biological processes, while oxidative stress denotes high levels of ROS that result in damage to DNA, protein or lipids. Thus, the response to ROS displays hormesis, given that the opposite effect is observed at low levels compared with that seen at high levels. Here, we argue that redox biology, rather than oxidative stress, underlies physiological and pathological conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            Reactive oxygen species in inflammation and tissue injury.

            Abstract Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury.
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              An epigenetic biomarker of aging for lifespan and healthspan

              Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.
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                Author and article information

                Contributors
                Journal
                Brain Commun
                Brain Commun
                braincomms
                Brain Communications
                Oxford University Press (US )
                2632-1297
                2024
                02 January 2024
                02 January 2024
                : 6
                : 1
                : fcad356
                Affiliations
                University of Exeter Medical School , Exeter, Devon EX2 4TH, UK
                Author notes
                Correspondence to: Annwyne Houldsworth E-mail: a.houldsworth@ 123456exeter.ac.uk
                Author information
                https://orcid.org/0009-0008-2660-6744
                Article
                fcad356
                10.1093/braincomms/fcad356
                10783645
                38214013
                38c70765-e8b5-41e1-9f5d-372f649e591f
                © The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 July 2023
                : 26 September 2023
                : 30 December 2023
                Page count
                Pages: 12
                Categories
                Review Article
                AcademicSubjects/MED00310
                AcademicSubjects/SCI01870

                superoxide dismutase,reactive oxygen species,alzheimer’s disease,neurodegeneration,avasopasem manganese

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