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.

中文翻译：

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阿尔茨海默病大脑、微血管系统和 NADPH 氧化酶

大脑微血管系统（尤其是海马体）的恶化似乎是阿尔茨海默病（AD）发展的一个非常早期的事件，甚至早于β淀粉样蛋白的沉积。受损的微脉管系统会减少该区域的氧气和葡萄糖供应，并限制能量 ATP 的产生。这种损伤可能是这些微血管中 NADPH 氧化酶 (NOX) 的表达和活性随着年龄的增长而增加的结果。这种上升使得这些血管容易受到氧化应激和炎症的影响。 NOX 活性随年龄的增长在 AD 大脑中更为明显，其中 NOX 活性与认知能力之间存在负相关关系。罗布麻素是一种公认​​的 NOX 抑制剂，已被证明可以阻止 NOX 活化的破坏作用。罗布麻宁是 H2O2 的强清除剂，也是超氧化物的弱清除剂。与罗布麻宁一样，羟丁酸钠 (SO) 也被证明可以阻止 NOX 活化的毒性作用。 SO 的应用产生NADPH 和ATP。 SO 抑制氧化应激并在缺氧条件下维持正常的脑 ATP 水平。此外，它还通过表观遗传作用减弱 NOX 的表达。 SO 可以通过整夜供应能量并维持大脑中的抗氧化环境来延迟 AD 的发作并减缓 AD 的进展。 SO 产生的慢波活性也可能激活类淋巴系统并促进大脑中β-淀粉样蛋白的清除。