Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23510, USA.
Department of Neurology, Eastern Virginia Medical School, Norfolk, VA 23510, USA.
Int J Mol Sci. 2022 Apr 8;23(8):4115. doi: 10.3390/ijms23084115.
Immune-inflammatory conditions in the central nervous system (CNS) rely on molecular and cellular interactions which are homeostatically maintained to protect neural tissue from harm. The CD40-CD40L interaction upregulates key proinflammatory molecules, a function best understood in the context of infection, during which B-cells are activated via CD40 signaling to produce antibodies. However, the role of CD40 in neurological disease of non-infectious etiology is unclear. We review the role of CD40-CD40L in traumatic brain injury, Alzheimer's Disease, Parkinson's Disease, stroke, epilepsy, nerve injury, multiple sclerosis, ALS, myasthenia gravis and brain tumors. We also highlight therapeutic advancements targeting the CD40 system to either attenuate the neuroinflammatory response or leverage the downstream effects of CD40 signaling for direct tumor cell lysis.
中枢神经系统(CNS)中的免疫炎症状态依赖于分子和细胞相互作用,这些相互作用通过维持体内平衡来保护神经组织免受伤害。CD40-CD40L 相互作用上调关键的促炎分子,这一功能在感染背景下最为人所理解,在此过程中,B 细胞通过 CD40 信号被激活以产生抗体。然而,CD40 在非传染性病因的神经疾病中的作用尚不清楚。我们综述了 CD40-CD40L 在创伤性脑损伤、阿尔茨海默病、帕金森病、中风、癫痫、神经损伤、多发性硬化症、肌萎缩侧索硬化症、重症肌无力和脑肿瘤中的作用。我们还强调了针对 CD40 系统的治疗进展,这些进展可以减轻神经炎症反应,或者利用 CD40 信号的下游效应直接裂解肿瘤细胞。