中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (8): 1223-1224.doi: 10.4103/1673-5374.162749

• 观点:退行性病与再生 • 上一篇    下一篇

抑制轴突功能以外的NOGO-A:帕金森病中的争议角色

  

  • 收稿日期:2015-06-18 出版日期:2015-08-24 发布日期:2015-08-24

Nogo-A and its functions beyond axonal inhibition: the controversial role of Nogo-A in Parkinson’s disease

Stefanie Seiler, Hans R. Widmer   

  1. Department of Neurosurgery, Neurocenter and Regenerative Neuroscience Cluster, University Hospital Bern, Switzerland University of Bern, Inselspital, Berne, Switzerland (Seiler S, Widmer HR)
    Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland (Seiler S)
  • Received:2015-06-18 Online:2015-08-24 Published:2015-08-24
  • Contact: Widmer, Ph.D., hanswi@insel.ch.
  • Supported by:

    This research was supported by the HANELA Foundation and the Swiss National Science Foundation (No. 31003A_135565).

摘要:

动物研究结果表明多巴胺神经元共同表达Nogo-A存活更好在帕金森病后期和更为显著的多巴胺细胞死亡帕金森Nogo-A基因敲除一样,强烈暗示Nogo-A对多巴胺神经细胞的神经保护作用,此外,与野生型小鼠相比,Nogo-A基因敲除小鼠有更好的运动协调以及全身苯丙胺注射增强的运动反应。安非他命增加多巴胺在突触间隙的释放,导致过度活跃的多巴胺解除对纹状的控制。这些结果表示,变异的多巴胺配合多巴胺基因敲除小鼠. Nogo-A在多巴胺神经细胞的功能需要进一步阐明特别是其信号功能。其他研究表明LINGO-1增加了帕金森病动物模型并阻碍了多巴胺神经元的存活。NgR1 或LINGO-1接触面咬合引起多巴胺神经细胞存活的增加,表明复杂的受体对于多巴胺神经细胞的存活有负面的调节作用。鉴于以上结果,Nogo-A在帕金森病中的潜在保护作用很可能不是由于Nogo-66领域信号穿过复杂受体。然而,Nogo-A如何保护多巴胺神经细胞 免受毒物侵害,如果还有其他的髓磷脂相关蛋白质,通过复杂受体如何调节多巴胺神经元生存还需要进一步调查。

Abstract:

The role and involvement of Nogo-A in Parkinson’s disease (PD) is just beginning to evolve. Even though none of the Nogo-A signaling genes has been associated with PD, the results from animal studies showing that DAergic neurons co-expressing Nogo-A survive better in the later course of PD as well as more pronounced DAergic cell death in PD Nogo-A knock-out animals hint strongly to a neuroprotective role of Nogo-A in DAergic neurons. Moreover, Nogo-A knock-out mice have a better motor coordination as well as an enhanced locomotor reaction to systemic amphetamine injections compared to wild type mice. The function of Nogo-A in DAergic neurons, however, needs to be further elucidates especially with focus on its signaling. After all, other studies showed that LINGO-1 is increased in animal models of PD and hampered the survival of DAergic neurons. Moreover, antagonization of NgR1 or LINGO-1 led to significant increase in survival of DAgeric neurons, showing that the NgR1 complex has a negative regulatory role on the survival of DAergic neurons. Considering these findings, the potential neuroprotective role of Nogo-A in PD is probably not due to the Nogo-66 domain that signals through the NgR1 complex. Yet, if and how Nogo-A protects DAergic neurons from toxic insults and if there are other myelin associated proteins that act through the NgR1complex as negative regulator of DAergic neuron survival needs to be further investigated.