中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (1): 73-74.doi: 10.4103/1673-5374.175045

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

神经鞘瘤提供损伤神经再生雪旺细胞p75NTR及merlin蛋白的研究新思路

  

  • 收稿日期:2016-01-04 出版日期:2016-01-15 发布日期:2016-01-15

Schwannomas provide insight into the role of p75NTR and merlin in Schwann cells following nerve injury and during regeneration

Elise Cheng, Marlan R. Hansen   

  1. Department of Otolaryngology – Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA (Cheng E, Hansen MR)
    Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA (Hansen MR)
  • Received:2016-01-04 Online:2016-01-15 Published:2016-01-15
  • Contact: Marlan R. Hansen, M.D.,marlan-hansen@uiowa.edu.
  • Supported by:

    This work is supported by T32 DC000040 and CDMRP NF130072.

摘要:

周围神经损伤导致断裂轴突的沃勒变性,雪旺细胞脱落,随之失神经的雪旺细胞或许会幸存下来并包围新生的轴突再生髓鞘。或者他们也可能会死亡。雪旺细胞的损失将严重阻碍细胞再生。最近,人们意外的对这种细胞因子作用机制有了更加深刻的认识。良性神经鞘瘤中的细胞生存信号,即:单个跨膜神经营养蛋白受体p75NTR 和膜骨架支架蛋白merlin通道的研究,为人们进一步了解失神经雪旺细胞的存活通路提供了新的思路。

Abstract:

Recent publications have begun to elucidate how merlin regulates responses of Schwann cells to nerve injury and how dysregulation of these responses in the absence of merlin likely contributes to schwannoma cell tumorigenesis. When Schwann cells lose contact with axons, merlin becomes phosphorylated leading to increased p75NTR expression and ultimately to schwannoma cell apoptosis and loss. However, in the absence of functional merlin, Schwann cells become resistant to p75NTR-mediated apoptosis. Further, p75NTR signaling elicits a prosurvival response in schwannoma cells, likely contributing to their ability to proliferate and survive in the absence of axons. This pro-survival response may contribute to the relative resistance of vestibular schwannomas cells to chemotherapeutic agents such as kinase inhibitors. Thus, simultaneously targeting p75NTR and/or NF-kB may sensitize vestibular schwannomas cells to other classes of chemotherapeutic agents. Interestingly, the mechanisms by which vestibular schwannomas cells escape cell death also inform our understanding of normal Schwann cell behavior following nerve injury.