中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (11): 1729-1730.doi: 10.4103/1673-5374.170294

• 观点:颅神经损伤修复保护与再生 • 上一篇    下一篇

脑蛋白氧化:反映了什么?

  

  • 收稿日期:2015-07-15 出版日期:2015-12-07 发布日期:2015-12-07

Brain protein oxidation: what does it reflect?

Parvana Hajieva, Bernd Moosmann*   

  1. Institute for Pathobiochemistry, University Medical Center of the
    Johannes Gutenberg University, Mainz, Germany
  • Received:2015-07-15 Online:2015-12-07 Published:2015-12-07
  • Contact: Bernd Moosmann, Ph.D.,moosmann@uni-mainz.de.

摘要:

大脑中蛋白质氧化很可能并非是由蛋白的特定脆弱性或暴露于氧化剂决定的,而是由它自身寿命决定,即在核糖体中从其合成延伸的时间窗长度到其在蛋白酶体或溶酶体中降解。由于人大脑皮层的特定轴突运输需求,该时间窗口在人类中可能非常长,这反过来又可以解释为什么人类与小鼠和大鼠相应蛋白质氧化会有如此显著不同的原因。这一结论结论为药物设计和未来研究带来了一些具体结果,以及一个新颖的想法,大脑蛋白质氧化可能与轴突运输(通过连接变量“蛋白质寿命”)相关。

Abstract:

Granted that the “oxidation-through-lifetime” hypothesis was correct, what consequences would emerge for future neuroprotective strategies? Most basically, humans and mice are different, even with respect to such fundamental aspects of redox homeostasis asprotein carbonyl formation. In humans, cytosolic protein oxidation appears to be much less of a problem than damage to membrane proteins, which might clearly account for the failure in humans of the exclusively aqueous double-sulfocompound NXY-059 that had been quite efficacious in rodents. Gyrencephalic animal models might provide some solution to avoid the rodent-human gap, as also mentioned in the STAIR recommendations for stroke, but it is clear that those are very much demanding. What could one still achieve in mice? Clearly, the study of protein turnover should provide significant insight. Moreover, the identification of proteins with very high baseline oxidation levels, or the search for proteins that are selectively degraded after an insult or in a disease might be more rewarding than the everlasting search for further proteins whose steady-state levels of oxidation are somewhat higher in a disease: the latter proteins might just reflect a selection of proteins whose oxidation is unusually well tolerated by the cell, such that it postpones their degradation to a later point. In the end, the study of protein oxidation in the dynamic context of turnover and site-specific degradation in the brain seems crucial, if only so for the realization of better treatment options for the primary proteolytic failure diseases.