蛋白激酶D2通过在缺血性中风中促进AKT和CREB激活来提供神经保护
Jaclyn A Connelly1, Xuejing Zhang1, Yuzhou Chen1
1Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, USA.
Neurobiology of disease
|September 20, 2023
概括
蛋白激酶D2 (PKD2) 在缺血性中风期间保护大脑细胞. 损失PKD2功能恶化了中风的结果,增加了神经元死亡,突出了PKD2功能.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 脑卒中研究 脑卒中研究
背景情况:
- 缺血性中风是导致死亡和残疾的主要原因.
- 迫切需要针对缺血性中风的新治疗点.
- 蛋白激酶D (PKD),特别是PKD2,在缺血性中风中的作用是不充分研究的.
研究的目的:
- 研究PKD2在缺血性中风中的作用.
- 确定PKD2是否具有神经保护作用.
- 在神经元生存中确定PKD2调节的信号通路.
主要方法:
- 在焦点脑缺血症后,测量了PKD2表达和脑组织中的活性.
- 使用酶死亡的PKD2敲进 (PKD2-KI) 鼠标和野生型 (WT) 鼠标接受中脑动脉封闭 (MCAO).
- 评估中风结果,包括心脏病发作量和神经学分数.
- 在PKD2-KI和WT小鼠的初级神经元中检查的神经元细胞死亡,在体外缺血症下.
- 确定了下游信号分子AKT和CREB.
主要成果:
- 在缺血性损伤后,PKD2表达和活动在大脑中增加.
- 与WT小鼠相比,PKD2-KI小鼠表现出较大的心脏病发作和较差的神经功能.
- 在缺血条件下,PKD2 缺陷的神经元表现出细胞死亡增加.
- 通过激活AKT和CREB信号通路,PKD2促进神经元的生存.
结论:
- 在缺血性中风中,PKD2起着神经保护作用.
- 激活PKD2可以防止缺血/再输血损伤.
- 向PKD2可能是缺血性中风的潜在治疗策略,以提高神经元的存活率.
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