Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by the presence of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles. Reduced antioxidants and increased oxidative stress and inflammation are responsible for the pathological features characteristic of an AD brain. We observed decreased levels of the reduced form of glutathione (GSH), the most abundant brain antioxidant, and decreased GSH/glutathione disulfide (GSSG) ratios in App^{NL−G-F/NL−G-F} knock-in (NL-G-F) mouse brains. Repeated oral GSH administration for 3 weeks dose-dependently increased GSH levels and restored the GSH/GSSH ratio. Consistent with the restoration of GSH levels, the levels of 4-hydroxy-2-nonenal (4-HNE), a marker of oxidative stress, were significantly decreased in the hippocampus of NL-G-F mice. Additionally, inflammatory responses, such as microgliosis and increased mRNA expression of inflammatory cytokines, were also inhibited. Moreover, behavioral deficits including cognitive decline, depressive-like behaviors, and anxiety-related behaviors observed in NL-G-F mice were significantly improved by oral and chronic GSH administration. Taken together, our data suggest that oral GSH administration is an attractive therapeutic strategy to reduce the excessive oxidative stress and inflammatory responses in the AD brain.

阿尔茨海默氏病（AD）是最常见的神经退行性疾病，其特征在于存在细胞外淀粉样β（Aβ）斑块和细胞内神经原纤维缠结。抗氧化剂的减少和氧化应激和炎症的增加是AD脑的病理特征。我们在App ^{NL-GF / NL-GF中}观察到还原型谷胱甘肽（GSH），最丰富的大脑抗氧化剂水平降低，并且GSH /谷胱甘肽二硫化物（GSSG）比降低敲入（NL-GF）小鼠的大脑。重复口服GSH 3周，剂量依赖性地增加了GSH水平，并恢复了GSH / GSSH比值。与GSH水平的恢复一致，NL-GF小鼠海马中4-羟基-2-壬烯醛（4-HNE）（氧化应激的标志物）的水平显着降低。另外，还抑制了炎症反应，例如小胶质细胞增生和炎症细胞因子的mRNA表达增加。此外，通过口服和长期服用GSH可以明显改善NL-GF小鼠的行为缺陷，包括认知能力下降，抑郁样行为和焦虑相关行为。在一起