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      Antioxidants as a Potential Target against Inflammation and Oxidative Stress in Attention-Deficit/Hyperactivity Disorder

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          Abstract

          Psychostimulants and non-psychostimulants are the medications prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD). However, several adverse results have been linked with an increased risk of substance use and side effects. The pathophysiology of ADHD is not completely known, although it has been associated with an increase in inflammation and oxidative stress. This review presents an overview of findings following antioxidant treatment for ADHD and describes the potential amelioration of inflammation and oxidative stress using antioxidants that might have a future as multi-target adjuvant therapy in ADHD. The use of antioxidants against inflammation and oxidative conditions is an emerging field in the management of several neurodegenerative and neuropsychiatric disorders. Thus, antioxidants could be promising as an adjuvant ADHD therapy.

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          Most cited references118

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          The emerging role of Nrf2 in mitochondrial function

          The transcription factor NF-E2 p45-related factor 2 (Nrf2; gene name NFE2L2) allows adaptation and survival under conditions of stress by regulating the gene expression of diverse networks of cytoprotective proteins, including antioxidant, anti-inflammatory, and detoxification enzymes as well as proteins that assist in the repair or removal of damaged macromolecules. Nrf2 has a crucial role in the maintenance of cellular redox homeostasis by regulating the biosynthesis, utilization, and regeneration of glutathione, thioredoxin, and NADPH and by controlling the production of reactive oxygen species by mitochondria and NADPH oxidase. Under homeostatic conditions, Nrf2 affects the mitochondrial membrane potential, fatty acid oxidation, availability of substrates (NADH and FADH2/succinate) for respiration, and ATP synthesis. Under conditions of stress or growth factor stimulation, activation of Nrf2 counteracts the increased reactive oxygen species production in mitochondria via transcriptional upregulation of uncoupling protein 3 and influences mitochondrial biogenesis by maintaining the levels of nuclear respiratory factor 1 and peroxisome proliferator-activated receptor γ coactivator 1α, as well as by promoting purine nucleotide biosynthesis. Pharmacological Nrf2 activators, such as the naturally occurring isothiocyanate sulforaphane, inhibit oxidant-mediated opening of the mitochondrial permeability transition pore and mitochondrial swelling. Curiously, a synthetic 1,4-diphenyl-1,2,3-triazole compound, originally designed as an Nrf2 activator, was found to promote mitophagy, thereby contributing to the overall mitochondrial homeostasis. Thus, Nrf2 is a prominent player in supporting the structural and functional integrity of the mitochondria, and this role is particularly crucial under conditions of stress.
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            ADHD in children and young people: prevalence, care pathways, and service provision

            Attention-deficit hyperactivity disorder (ADHD) is a common childhood behavioural disorder. Systematic reviews indicate that the community prevalence globally is between 2% and 7%, with an average of around 5%. At least a further 5% of children have substantial difficulties with overactivity, inattention, and impulsivity that are just under the threshold to meet full diagnostic criteria for ADHD. Estimates of the administrative prevalence (clinically diagnosed or recorded) vary worldwide, and have been increasing over time. However, ADHD is still relatively under-recognised and underdiagnosed in most countries, particularly in girls and older children. ADHD often persists into adulthood and is a risk factor for other mental health disorders and negative outcomes, including educational underachievement, difficulties with employment and relationships, and criminality. The timely recognition and treatment of children with ADHD-type difficulties provides an opportunity to improve long-term outcomes. This Review includes a systematic review of the community and administrative prevalence of ADHD in children and adolescents, an overview of barriers to accessing care, a description of associated costs, and a discussion of evidence-based pathways for the delivery of clinical care, including a focus on key issues for two specific age groups-younger children (aged ≤6 years) and adolescents requiring transition of care from child to adult services.
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              Neuroinflammation pathways: a general review.

              Activated microglial cells play an important role in immune and inflammatory responses in central nervous system and neurodegenerative diseases. Many pro-apoptotic pathways are mediated by signaling molecules that are produced during neuroinflammation. In glial cells, NF-κB, a transcription factor, initiates and regulates the expression of several inflammatory processes during inflammation which are attributed to the pathology of the several neurodegenerative diseases. In this review, we discuss the most important neuroinflammatory mediators with their pathways. Attenuating cytokines production and controlling microglial inflammatory response, which are the result of understanding neuroinflammation pathways, are considered therapeutic strategies for treating neurodegenerative diseases with an inflammatory component.
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                Author and article information

                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                21 February 2020
                February 2020
                : 9
                : 2
                : 176
                Affiliations
                [1 ]CONACYT-Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; lourdes.alvareza@ 123456gmail.com
                [2 ]Laboratory of Neurosciences, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; nadiag.him@ 123456gmail.com
                [3 ]Laboratorio de Investigación en Biología del Desarrollo y Teratogénesis Experimental, Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico; msalazar.investigacion@ 123456gmail.com
                Author notes
                [* ]Correspondence: jcorona@ 123456himfg.edu.mx ; Tel.: +52-(55)-52289917
                Author information
                https://orcid.org/0000-0002-3469-1407
                https://orcid.org/0000-0003-4907-437X
                Article
                antioxidants-09-00176
                10.3390/antiox9020176
                7070894
                32098021
                b0d80a24-083c-4e73-9174-9dfe948a9018
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 December 2019
                : 30 January 2020
                Categories
                Review

                antioxidants,adhd,inflammation,oxidative stress,nrf2
                antioxidants, adhd, inflammation, oxidative stress, nrf2

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