Keane Robert W, Davis Angela R, Dietrich W Dalton
Department of Physiology and Biophysics, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
J Neurotrauma. 2006 Mar-Apr;23(3-4):335-44. doi: 10.1089/neu.2006.23.335.
Central nervous system (CNS) destruction in spinal cord injury (SCI) is caused by a complex series of cellular and molecular events. Recent studies have concentrated on signaling by receptors in the tumor necrosis factor receptor (TNFR) superfamily that mediate diverse biological outcomes ranging from inflammation to apoptosis. From the perspective of basic science research, understanding how receptor signaling mediates these divergent responses is critical in clarifying events underlying irreversible cell injury in clinically relevant models of SCI. From a clinical perspective, this work also provides novel targets for the development of therapeutic agents that have the potential to protect the spinal cord from irreversible damage and promote functional recovery. In this review, we discuss how the formation of alternate signaling complexes and receptor membrane localization after SCI can influence life and death decisions of cells stimulated through two members of the TNFR superfamily, Fas/CD95 and TNFR1.
脊髓损伤（SCI）中中枢神经系统（CNS）的破坏是由一系列复杂的细胞和分子事件引起的。最近的研究集中在肿瘤坏死因子受体（TNFR）超家族中的受体信号传导上，这些受体介导从炎症到细胞凋亡等多种生物学结果。从基础科学研究的角度来看，了解受体信号如何介导这些不同的反应对于阐明SCI临床相关模型中不可逆细胞损伤的潜在机制至关重要。从临床角度来看，这项工作还为开发治疗药物提供了新的靶点，这些药物有可能保护脊髓免受不可逆损伤并促进功能恢复。在这篇综述中，我们讨论了SCI后交替信号复合物的形成和受体膜定位如何影响通过TNFR超家族的两个成员Fas/CD95和TNFR1刺激的细胞的生死抉择。
