Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
J Neuroimmune Pharmacol. 2012 Mar;7(1):42-59. doi: 10.1007/s11481-011-9287-2. Epub 2011 Jul 5.
Tumor Necrosis Factor-alpha (TNF-α) is a prototypic pro-inflammatory cytokine involved in the innate immune response. TNF-α ligation and downstream signaling with one of its cognate receptors, TNF-RI or TNF-RII, modulates fundamental processes in the brain including synapse formation and regulation, neurogenesis, regeneration, and general maintenance of the central nervous system (CNS). During states of chronic neuroinflammation, extensive experimental evidence implicates TNF-α as a key mediator in disease progression, gliosis, demyelination, inflammation, blood-brain-barrier deterioration, and cell death. This review explores the complex roles of TNF-α in the CNS under normal physiologic conditions and during neurodegeneration. We focus our discussion on Multiple Sclerosis, Parkinson's disease, and Alzheimer's disease, relaying the outcomes of preclinical and clinical testing of TNF-α directed therapeutic strategies, and arguing that despite the wealth of functions attributed to this central cytokine, surprisingly little is known about the cell type- and stage-specific roles of TNF-α in these debilitating disorders.
肿瘤坏死因子-α（TNF-α）是一种典型的前炎性细胞因子，参与固有免疫反应。TNF-α与其同源受体 TNF-RI 或 TNF-RII 的结合及其下游信号转导，调节大脑中的基本过程，包括突触形成和调节、神经发生、再生以及中枢神经系统（CNS）的一般维持。在慢性神经炎症状态下，大量实验证据表明 TNF-α 是疾病进展、神经胶质增生、脱髓鞘、炎症、血脑屏障恶化和细胞死亡的关键介质。本综述探讨了 TNF-α 在正常生理条件下和神经退行性变过程中在中枢神经系统中的复杂作用。我们重点讨论多发性硬化症、帕金森病和阿尔茨海默病，阐述了针对 TNF-α 的治疗策略的临床前和临床研究结果，并认为尽管该中枢细胞因子具有丰富的功能，但对于 TNF-α 在这些使人衰弱的疾病中的细胞类型和阶段特异性作用却知之甚少。
