在神经发育障碍中,对神经递质受体具有结合 afinity 的血脑屏障透微生物组代谢物的计算识别
Ricardo E Buendia-Corona1, María Fernanda Velasco Dey2, Lisset Valencia Robles2
1Departamento de Ciencias Químico-Biológicas, Universidad de las Américas Puebla, Puebla 72810, Mexico.
Molecules (Basel, Switzerland)
|January 28, 2026
概括
这项研究揭示了真菌代谢物可以穿越血脑屏障并与神经递质受体相互作用,为图雷特综合征等神经发育障碍提供新的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 微生物组研究的研究.
- 计算化学是一种计算化学.
背景情况:
- 肠道微生物群通过代谢物影响中枢神经系统 (CNS) 功能.
- 神经递质失调和微生物组变化在图雷特综合征,多动症和ASD中被观察到.
- 微生物代谢物和神经调节之间的机制联系尚未完全理解.
研究的目的:
- 为了识别能够穿越血脑屏障 (BBB) 的肠道微生物代谢物.
- 研究这些代谢物与关键神经递质受体之间的相互作用.
- 探索真菌代谢物在神经发育障碍的神经调节中的潜力.
主要方法:
- 通过使用SwissADME和PyTorch神经网络,选了27,642种微生物代谢物的BBB透性.
- 对五个神经递质受体 (GABRA2,GRIA2,GRIN2B,DRD4,HTR1A) 进行了分子对接.
- 优化了代谢物构造,并根据可旋转的纽带进行定制,用于对接.
主要成果:
- 确定了1696 (SwissADME) 和2484 (PyTorch) 的BBB交叉代谢物.
- 排名前50位的联体显示了方法特定的BBB分类,突出了补充性预测方法.
- 来自*Ascomycota*的真菌代谢物 (66%) 主导着高亲缘关系的配体,而Menaquinone MK-7显示了广泛的保存.
结论:
- 建立了详细的受体-代谢物相互作用地图,其中真菌代谢物起着重要作用.
- 挑战了在微生物组研究中对细菌代谢物的传统关注.
- 提供了针对神经发育障碍的微生物组向治疗的基础.
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