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Issue title: Pro-Oxidants and Antioxidants in Alzheimer’s Disease
Guest editors: Pravat K. Mandal
Article type: Review Article
Authors: Mamelak, Mortimer; *
Affiliations: Department of Psychiatry, Baycrest Hospital, University of Toronto, Toronto, Ontario, Canada
Correspondence: [*] Correspondence to: Mortimer Mamelak, MD, FRCP(C), Baycrest Hospital, University of Toronto, Department of Psychiatry, Toronto, Ontario M6A 2E1, Canada. Tel.: +1 416 493 5421; +1 416 931 7230; E-mail: [email protected].
Abstract: The deterioration of the brain’s microvasculature, particularly in the hippocampus, appears to be a very early event in the development of Alzheimer’s disease (AD), preceding even the deposition of amyloid-β. A damaged microvasculature reduces the supply of oxygen and glucose to this region and limits the production of energy, ATP. The damage may be a function of the rise with age in the expression and activity of NADPH oxidase (NOX) in these microvessels. This rise renders these vessels vulnerable to the effects of oxidative stress and inflammation. The rise in NOX activity with age is even more marked in the AD brain where an inverse correlation has been demonstrated between NOX activity and cognitive ability. Apocynin, a putative NOX inhibitor, has been shown to block the damaging effects of NOX activation. Apocynin acts as a strong scavenger of H2O2, and as a weak scavenger of superoxide. Like apocynin, sodium oxybate (SO) has also been shown to block the toxic effects of NOX activation. The application of SO generates NADPH and ATP. SO inhibits oxidative stress and maintains normal cerebral ATP levels under hypoxic conditions. Moreover, it acts epigenetically to attenuate the expression of NOX. SO may delay the onset and slow the progress of AD by suppling energy and maintaining an antioxidative environment in the brain throughout the night. The slow wave activity produced by SO may also activate the glymphatic system and promote the clearance of amyloid-β from the brain.
Keywords: Alzheimer’s disease, amyloid-β , apocynin, cerebral microvasculature, NADPH, NADPH oxidase, oxidative stress, sodium oxybate
DOI: 10.3233/JAD-230415
Journal: Journal of Alzheimer's Disease, vol. 99, no. s1, pp. S109-S118, 2024
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