中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (9): 1403-1405.doi: 10.4103/1673-5374.165505

• 观点:退行性病与再生 • 上一篇    下一篇

神经肽P物质及其NK1速激肽受体:帕金森病神经保护新的靶点?

  

  • 收稿日期:2015-08-10 出版日期:2015-09-28 发布日期:2015-09-28

Substance P and its tachykinin NK1 receptor: a novel neuroprotective target for Parkinson’s disease

Emma Thornton, Robert Vink   

  1. School of Medical Sciences, University of Adelaide, Adelaide, Australia; Division of Health Sciences, University of South Australia, Adelaide, Australia
  • Received:2015-08-10 Online:2015-09-28 Published:2015-09-28
  • Contact: Robert Vink, Ph.D., Robert.Vink@unisa.edu.au.
  • Supported by:

    This work has been presented at the International Congress of Parkinson’s Disease and Movement Disorders (2009 and 2010), and in part has been supported by the Neurosurgical Research Foundation, South Australia, Australia. The authors would like to thank Tavik Morgenstern for assistance with the Figure 1 graphics.

摘要:

神经肽P物质可提高血脑屏障通透性,随即增加外周免疫细胞浸润,以及激活驻留的免疫细胞。这些损伤级联反应不仅直接导致帕金森病多巴胺能神经元的持续神经变性,也会加剧如氧化应激和线粒体功能障碍等其他继发性损伤。神经肽P物质诱发神经原性炎症在帕金森病的发病机制中起着重要的作用。NK1-R拮抗剂可缓解帕金森病的进展,显著降低诱发运动障碍的发生,这可能是通过抑制涉及神经肽P物质和NK1速激肽受体多因素损伤的结果有关。根据阻断神经肽P物质与NK1-R拮抗剂的作用,可设计开发出一种新的用于帕金森病神经保护的治疗药物。

Abstract:

Substance P-induced neurogenic inflammation may play an important role in the pathogenesis of Parkinson’s disease (PD), including L-DOPA induced dyskinesia (LID), by increasing BBB permeability and subsequent peripheral immune cell infiltration, as well as activation of resident immune cells. These injury cascades not only directly contribute to the ongoing neurodegeneration of dopaminergic neurons in PD but can also exacerbate other secondary injury mechanisms such as oxidative stress and mitochondrial dysfunction. Treatment with an NK1-R antagonist attenuated the progression of PD and significantly reduced the onset of LID, presumably by inhibiting multifactorial injury mechanisms involving SP and NK1-R. Blocking the effects of SP with a NK1-R antagonist therefore presents a potentially promising new avenue for neuroprotection in PD.