在脑缺血中解读尼特洛克索林的神经保护机制:基于网络药理学和分子建模的研究
Namrata Vadak1, Maheshkumar R Borkar2, Lokesh Kumar Bhatt3
1Department of Pharmacology, SVKM's Dr Bhanuben, Nanavati College of Pharmacy, Vile Parle (W), Mumbai, India.
Molecular diversity
|January 17, 2024
概括
尼特罗克索林通过调节关键通路和目标,如BRD4,显示其作为神经保护剂的潜力,以防止脑缺血. 需要进一步的研究来证实它在治疗这种疾病中的有效性.
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.
- 计算生物学 计算生物学
背景情况:
- 脑缺血是全球死亡和残疾的主要原因.
- 目前的治疗重点是再注射,突出了对神经保护药物的未满足需求.
- 尼特洛克索林是8-氧基诺林的基衍生物,因其潜在的神经保护性质而受到探索.
研究的目的:
- 为了研究氧对脑缺血的神经保护机制.
- 利用集成网络药理学和分子对接方法来识别目标.
- 探索氧在调节临界生物过程和涉及缺血损伤的途径中的作用.
主要方法:
- 使用多个数据库 (SwissTarget,PharmMapper,BindingDB,DisGeNet) 和工具 (Cytoscape,GeneMANIA,ShinyGo,Metascape,GeneCodis) 进行网络药理学分析.
- 识别重叠的药物和疾病目标.
- 使用施罗丁格GLIDE进行分子对接和动态模拟以验证目标.
- 基因本体学和KEGG丰富分析.
主要成果:
- 确定了36个重叠的目标,富含氧化应激和细胞死亡途径.
- 尼트로林影响了159个途径,包括长寿调节,VEGF信号传递和HIF-1途径.
- 分子对接显示,尼特洛克索林与BRD4的结合亲和力最高,其次是PARP1和PTEN.
结论:
- 尼트로克索林通过网络药理学证明了对脑缺血的潜在神经保护作用.
- 它可能通过调节表观遗传阅读器BRD4和转录因子如RELA,NF-κβ1和SP1.1来发挥其作用.
- 需要进一步的体外和临床前研究来验证这些发现,并确定氧的治疗潜力.
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