对血管认知障碍的希望:Ac-YVAD-cmk作为一种针对白质稀缺的新疗法
Yun-An Lim1, Li Si Tan1, Wei Thye Lee1
1Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
PloS one
|April 17, 2024
概括
用Ac-YVAD-cmk抑制caspase-1,在患有血管认知障碍 (VCI) 的小鼠模型中改善了大脑血流和减少了白质稀缺. 这表明对皮下VCI的潜在治疗益处.
科学领域:
- 神经科学是一个神经科学.
- 血管生物学 血管生物学
- 痴呆症研究 痴呆症研究
背景情况:
- 血管认知障碍 (VCI) 是痴呆的主要原因,其特点是大脑血流减少和白质损伤.
- 皮下VCI是常见的,但其特定脆弱性的原因尚未完全理解.
- 炎症酶,特别是NLRP3/caspase-1,与白质损伤有关,但caspase-1抑制的有效性尚不清楚.
研究的目的:
- 为了研究Ac-YVAD-cmk的治疗潜力,一个caspase-1抑制剂,在VCI的小鼠模型中.
- 确定caspase-1抑制对大脑血液流动,白质稀少以及皮层下和皮层区域血脑屏障完整性的影响.
主要方法:
- 双边皮层动脉狭窄 (BCAS) 在小鼠中被诱导.
- 小鼠接受了Ac-YVAD-cmk的治疗.
- 评估了大脑血流 (CBF),白质稀缺 (WMR),神经炎症和紧结蛋白表达.
主要成果:
- 治疗Ac-YVAD-cmk恢复了CBF,减轻了WMR和皮下区域的髓损失.
- 在BCAS后的皮下区域激活了NLRP3/caspase-1/interleukin-1beta通路,并被Ac-YVAD-cmk抑制.
- 在皮下区域,Ac-YVAD-cmk降低了VCAM-1的表达,并使ZO-1和奥克卢丁水平正常化.
结论:
- 卡斯帕斯-1在皮下区域对与VCI相关的损伤的敏感性中起作用.
- 作为潜在的治疗剂,Ac-YVAD-cmk在皮层下VCI和涉及大脑低 perfusion 的相关疾病中表现有前途.
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