Aebischer Julianne, Bernard-Marissal Nathalie, Pettmann Brigitte, Raoul Cédric
Inserm-Avenir team, The Mediterranean Institute of Neurobiology (INMED), 13288 Marseille, France ; Neurodegenerative Studies Laboratory, Brain Mind Institute, The Swiss Federal Institute of Technology Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Inserm-Avenir team, The Mediterranean Institute of Neurobiology (INMED), 13288 Marseille, France ; Department of Medical Genetics, University of Lausanne, CH-1005 Lausanne, Switzerland.
J Neurodegener Dis. 2013;2013:746845. doi: 10.1155/2013/746845. Epub 2013 Jul 16.
While studies on death receptors have long been restricted to immune cells, the last decade has provided a strong body of evidence for their implication in neuronal death and hence neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). ALS is a fatal paralytic disorder that primarily affects motoneurons in the brain and spinal cord. A neuroinflammatory process, associated with astrocyte and microglial activation as well as infiltration of immune cells, accompanies motoneuron degeneration and supports the contribution of non-cell-autonomous mechanisms in the disease. Hallmarks of Fas, TNFR, LT-βR, and p75(NTR) signaling have been observed in both animal models and ALS patients. This review summarizes to date knowledge of the role of death receptors in ALS and the link existing between the selective loss of motoneurons and neuroinflammation. It further suggests how this recent evidence could be included in an ultimate multiapproach to treat patients.
虽然长期以来关于死亡受体的研究一直局限于免疫细胞，但在过去十年中，已有大量有力证据表明它们与神经元死亡有关，进而与诸如肌萎缩侧索硬化症（ALS）等神经退行性疾病相关。ALS是一种致命的麻痹性疾病，主要影响大脑和脊髓中的运动神经元。一种与星形胶质细胞和小胶质细胞激活以及免疫细胞浸润相关的神经炎症过程伴随着运动神经元的退化，并支持非细胞自主机制在该疾病中的作用。在动物模型和ALS患者中均观察到Fas、TNFR、LT-βR和p75（NTR）信号通路的特征。本综述总结了迄今为止关于死亡受体在ALS中的作用以及运动神经元选择性丧失与神经炎症之间存在的联系的知识。它还进一步提出了如何将这一最新证据纳入最终的多方法治疗患者方案中。
