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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

阿尔茨海默病脑IDO抑制靶点参与模型的建立与优化

卷 20, 期 10, 2023

发表于: 26 January, 2024

页: [705 - 714] 页: 10

弟呕挨: 10.2174/0115672050283199240111111801

价格: $65

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摘要

背景:吲哚胺2,3-双加氧酶(IDO1)抑制是阿尔茨海默病(AD)疾病修饰治疗的一个有希望的靶点，能够下调免疫病理神经炎症过程。 方法:为了帮助开发IDO抑制剂作为潜在的AD治疗药物，我们通过腹腔注射检测脑犬尿氨酸:色氨酸(K:T)与LPS的剂量依赖性和时间过程，优化了基于脂多糖(LPS)的脑IDO1抑制小鼠模型。 结果:我们确定了提高脑内IDO1活性的最佳LPS剂量，以及量化LPS给药后脑K:T比值的理想时间点。然后，我们使用脑渗透工具化合物EOS200271来验证模型，确定最佳剂量配置，并发现该工具化合物可以完全挽救K:T比。 结论:基于LPS的IDO1靶点结合模型可用于开发脑渗透性IDO1 AD抑制剂。本研究的一个局限性是该模型中缺乏潜在临床相关生物标志物的量化，这可以在未来的研究中解决。

关键词: 阿尔茨海默病，吲哚胺2,3-双加氧酶，脂多糖，药理学，犬尿氨酸，色氨酸。

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