Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases

Non-communicable neurological disorders are the second leading cause of death, and their burden continues to increase as the world population grows and ages. Oxidative stress and inflammation are crucially implicated in the triggering and progression of multiple sclerosis, Alzheimer’s disease, amyot...

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Main Authors: Massimo Bortolotti, Letizia Polito, Maria Giulia Battelli, Andrea Bolognesi
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/14/4/483
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author Massimo Bortolotti
Letizia Polito
Maria Giulia Battelli
Andrea Bolognesi
author_facet Massimo Bortolotti
Letizia Polito
Maria Giulia Battelli
Andrea Bolognesi
author_sort Massimo Bortolotti
collection DOAJ
description Non-communicable neurological disorders are the second leading cause of death, and their burden continues to increase as the world population grows and ages. Oxidative stress and inflammation are crucially implicated in the triggering and progression of multiple sclerosis, Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, Parkinson’s disease, and even stroke. In this narrative review, we examine the role of xanthine oxidoreductase (XOR) activities and products in all the above-cited neurological diseases. The redox imbalance responsible for oxidative stress could arise from excess reactive oxygen and nitrogen species resulting from the activities of XOR, as well as from the deficiency of its main product, uric acid (UA), which is the pivotal antioxidant system in the blood. In fact, with the exception of stroke, serum UA levels are inversely related to the onset and progression of these neurological disorders. The inverse correlation observed between the level of uricemia and the presence of neurological diseases suggests a neuroprotective role for UA. Oxidative stress and inflammation are also caused by ischemia and reperfusion, a condition in which XOR action has been recognized as a contributing factor to tissue damage. The findings reported in this review could be useful for addressing clinical decision-making and treatment optimization.
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spelling doaj-art-38f9f0bfe7ad49bbabec6d9fa30040b32025-08-20T03:14:16ZengMDPI AGAntioxidants2076-39212025-04-0114448310.3390/antiox14040483Xanthine Oxidoreductase: A Double-Edged Sword in Neurological DiseasesMassimo Bortolotti0Letizia Polito1Maria Giulia Battelli2Andrea Bolognesi3Department of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum, University of Bologna, Via San Giacomo 14, 40126 Bologna, ItalyDepartment of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum, University of Bologna, Via San Giacomo 14, 40126 Bologna, ItalyDepartment of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum, University of Bologna, Via San Giacomo 14, 40126 Bologna, ItalyDepartment of Medical and Surgical Sciences—DIMEC, Alma Mater Studiorum, University of Bologna, Via San Giacomo 14, 40126 Bologna, ItalyNon-communicable neurological disorders are the second leading cause of death, and their burden continues to increase as the world population grows and ages. Oxidative stress and inflammation are crucially implicated in the triggering and progression of multiple sclerosis, Alzheimer’s disease, amyotrophic lateral sclerosis, Huntington’s disease, Parkinson’s disease, and even stroke. In this narrative review, we examine the role of xanthine oxidoreductase (XOR) activities and products in all the above-cited neurological diseases. The redox imbalance responsible for oxidative stress could arise from excess reactive oxygen and nitrogen species resulting from the activities of XOR, as well as from the deficiency of its main product, uric acid (UA), which is the pivotal antioxidant system in the blood. In fact, with the exception of stroke, serum UA levels are inversely related to the onset and progression of these neurological disorders. The inverse correlation observed between the level of uricemia and the presence of neurological diseases suggests a neuroprotective role for UA. Oxidative stress and inflammation are also caused by ischemia and reperfusion, a condition in which XOR action has been recognized as a contributing factor to tissue damage. The findings reported in this review could be useful for addressing clinical decision-making and treatment optimization.https://www.mdpi.com/2076-3921/14/4/483xanthine oxidoreductaseuric acidneurodegenerative diseasesstrokeoxidative stressinosine
spellingShingle Massimo Bortolotti
Letizia Polito
Maria Giulia Battelli
Andrea Bolognesi
Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases
Antioxidants
xanthine oxidoreductase
uric acid
neurodegenerative diseases
stroke
oxidative stress
inosine
title Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases
title_full Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases
title_fullStr Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases
title_full_unstemmed Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases
title_short Xanthine Oxidoreductase: A Double-Edged Sword in Neurological Diseases
title_sort xanthine oxidoreductase a double edged sword in neurological diseases
topic xanthine oxidoreductase
uric acid
neurodegenerative diseases
stroke
oxidative stress
inosine
url https://www.mdpi.com/2076-3921/14/4/483
work_keys_str_mv AT massimobortolotti xanthineoxidoreductaseadoubleedgedswordinneurologicaldiseases
AT letiziapolito xanthineoxidoreductaseadoubleedgedswordinneurologicaldiseases
AT mariagiuliabattelli xanthineoxidoreductaseadoubleedgedswordinneurologicaldiseases
AT andreabolognesi xanthineoxidoreductaseadoubleedgedswordinneurologicaldiseases