来自Bacopa monnieri的植物化学物质作为MARK4的小分子调节剂:防止导致阿尔茨海默病的tau聚合的多模式策略
S Rehan Ahmad1, Md Zeyaullah2, Yousef Zahrani3
1Hiralal Mazumdar Memorial College for Women, West Bengal State University, Kolkata, West Bengal, 700035, India.
Journal of molecular graphics & modelling
|August 7, 2025
概括
巴科巴蒙尼耶里化合物,如奥洛克辛丁,作为MARK4的天然抑制剂显示出希望,这是阿尔茨海默病病理学的关键酶. 这些植物化学物质有效地减少细胞中的陶聚合物,为神经退行性陶病提供了潜在的新疗法.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 生物化学 生物化学
背景情况:
- 包括阿尔茨海默氏症在内的神经退行性陶氏病与异常的陶氏酸化有关.
- 氨酸/氨酸激酶MARK4在陶酸化中起着调节作用.
研究的目的:
- 研究Bacopa monnieri中的植物化学物质作为MARK4.4的潜在天然抑制剂.
- 评估这些化合物在减少病理方面的有效性.
主要方法:
- 压力液体提取和LC-MS用于从Bacopa monnieri.中化合物识别.
- 在基分子对接中,分子动力学模拟和微观温度测试用于结合亲和力.
- 细胞毒性的MTT测定和tau总量减少的细胞测定.
主要成果:
- 确定了25种植物成分,包括黄类,三类和类.
- 奥洛克辛丁,库库比他素B和巴科辛对MARK4的催化口袋表现出强烈的结合.
- 奥洛辛丁显示出最佳的结合稳定性;五种化合物显示出高亲和度结合.
- 化合物是非细胞毒性的,并且在SH-SY5Y细胞中显著减少了Tau-GFP聚合物.
结论:
- 奥洛辛丁和其他Bacopa monnieri植物化学物质是MARK4.4的强有力的天然抑制剂.
- 这些化合物有可能减轻像阿尔茨海默氏症这样的神经退行性疾病中的tau病理.
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