暂时受体潜在的化物通道2有助于多模态内质网膜和周核空间扩张,这种扩张也可以在受感染的小鼠中观察到
Wenda Zhao1,2, Shehab Eid1,2, Chris Sackmann1
1Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
研究人员探索了心脏葡萄糖化物中毒和病真空化之间的相似之处. 他们发现,涉及TRPV2和PIKFYVE的内等质网膜扩张可能会导致形变性在普里翁疾病中.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 历史数据表明,心脏糖化物 (CG) 中毒和病真空化表型之间存在相似之处.
- 以前的研究驳斥了这种联系,原因是受影响细胞 (星细胞与神经元) 的差异.
研究的目的:
- 为了研究 prion 疾病中真空化背后的细胞机制.
- 为了确定细胞内膜网膜 (ER) 扩张是否在海绵状变性中起作用.
- 探索Na+,K+-ATPases (NKAs),TRPV2和PIKFYVE在ER真空化中的参与.
主要方法:
- 使用动物模型与人性化的NKA α1子单元.
- 在各种压力因素下,研究了人体细胞中的ER真空化在体外.
- 使用的药理学剂,离子特异性染料,抗剂和截断表达结构.
- 分析了子感染小鼠的冷切割大脑.
主要成果:
- 在表达人性化NKAα1子单元的小鼠中,真空转移到神经元.
- 过度表达NKA子单元或毒素诱导ER和周核空间 (PNS) 扩张,独立于离子失衡.
- 有证据表明,短暂受体潜在瓦尼洛伊德2 (TRPV2) 通道介导ER/PNS扩张.
- 空腔形成与降低PIKFYVE水平相关.
- 在被子感染的小鼠大脑中观察到空腔,这些大脑是ER/PNS标记物的目标.
结论:
- 可能由TRPV2调解并与PIKFYVE减小相关的ER和PNS扩张是一种在病模型中观察到的新型表型.
- 这种真空化现象可能有助于型变性特征的病.
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