Kristina A Mukhina, Olga I Kechko, Alexander A Osypov, Irina Yu Petrushanko, Alexander A Makarov, Vladimir A Mitkevich, Irina Yu Popova
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Short-Term Inhibition of NOX2 Prevents the Development of Aβ-Induced Pathology in Mice.
Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by the formation of neurotoxic beta-amyloid (Aβ) oligomers in the central nervous system. One of the earliest pathological effects of Aβ is the induction of oxidative stress in brain tissue, mediated by NADPH oxidase 2 (NOX2). This study aimed to determine whether short-term inhibition of NOX2 could disrupt the pathological cascade and prevent the development of Aβ-induced pathology. We demonstrated that suppressing NOX2 activity by GSK2795039 during the first three days after intracerebral Aβ administration prevented the development of the pathological process in mice. Two weeks after the induction of Aβ pathology, animals treated with GSK2795039 showed no neuropsychiatric-like behavioral changes, which correlated with the absence of chronic oxidative damage in brain tissue. Moreover, GSK2795039 prevented microglial activation and reduced microglia-associated neuroinflammation. These findings indicate that short-term NOX2 inhibition effectively suppresses the development of Aβ-induced pathology, suggesting that NOX2 is a potential target for treatment and prevention of AD pathology.
AntioxidantsBiochemistry, Genetics and Molecular Biology-Physiology
CiteScore
10.60
自引率
11.40%
发文量
2123
审稿时长
16.3 days
期刊介绍:
Antioxidants (ISSN 2076-3921), provides an advanced forum for studies related to the science and technology of antioxidants. It publishes research papers, reviews and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.