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经TAT修改的马丁毒素显示了静脉注射抗发作活动
Huan Liu1,2, Dongxiao Qu3, Yunzhu Cao2,4
1School of pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
经过静脉注射后,修改的Martentoxin (MarTX) ,MTX-C-TAT,有效地穿越了血脑屏障 (BBB),在模型中显示出显著的抗发作活性和神经保护.
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 生化学
背景情况:
- 是一种慢性神经系统疾病,由于神经回路失衡而导致经常性发作.
- 来自Buthus martensii Karsch的胺Martentoxin (MarTX) 通过抑制BK(α + β4) 通道表现出抗发作特性,但在穿越血脑屏障 (BBB) 方面面临挑战.
研究的目的:
- 开发MarTX的细胞透 (CPP) 修改,以提高其穿越BBB的能力,用于静脉注射.
- 评估TAT修饰的MarTX变体 (MTX-N-TAT和MTX-C-TAT) 的抗发作疗效和神经保护作用.
主要方法:
- 使用大肠杆菌过度表达系统设计和合成了TAT结合的MarTX变体 (MTX-N-TAT和MTX-C-TAT).
- 静脉注射了MTX-C-TAT,并评估了它对发作迟缓,持续时间,严重程度,神经元过敏性和神经保护的影响.
主要成果:
- 静脉注射MTX-C-TAT显示出对抗发作的显著治疗效果.
- MTX-C-TAT增加了发作的延迟时间,减少了发作的持续时间和严重程度,并抑制了海马神经元的过度兴奋性.
- 观察到对海马神经元的神经保护作用,表明BBB透和治疗潜力.
结论:
- 在静脉注射后,MTX-C-TAT有效地穿越BBB,表现出强大的抗发作活性.
- 经TAT修饰的MarTX,特别是MTX-C-TAT,代表了治疗的有前途的治疗候选者.
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