Department of Anesthesiology, Duke University Medical Center, Durham, 27710, USA.
Department of Biology, Duke University Medical Center, Durham, 27710, USA.
Neurosci Bull. 2021 Aug;37(8):1188-1202. doi: 10.1007/s12264-021-00683-y. Epub 2021 Apr 20.
Programmed cell death protein 1 (PD-1) is an immune checkpoint modulator and a major target of immunotherapy as anti-PD-1 monoclonal antibodies have demonstrated remarkable efficacy in cancer treatment. Accumulating evidence suggests an important role of PD-1 in the central nervous system (CNS). PD-1 has been implicated in CNS disorders such as brain tumors, Alzheimer's disease, ischemic stroke, spinal cord injury, multiple sclerosis, cognitive function, and pain. PD-1 signaling suppresses the CNS immune response via resident microglia and infiltrating peripheral immune cells. Notably, PD-1 is also widely expressed in neurons and suppresses neuronal activity via downstream Src homology 2 domain-containing protein tyrosine phosphatase 1 and modulation of ion channel function. An improved understanding of PD-1 signaling in the cross-talk between glial cells, neurons, and peripheral immune cells in the CNS will shed light on immunomodulation, neuromodulation, and novel strategies for treating brain diseases.
程序性细胞死亡蛋白 1（PD-1）是一种免疫检查点调节剂，也是免疫疗法的主要靶点，因为抗 PD-1 单克隆抗体在癌症治疗中显示出了显著的疗效。越来越多的证据表明 PD-1 在中枢神经系统（CNS）中起着重要作用。PD-1 与 CNS 疾病有关，如脑肿瘤、阿尔茨海默病、缺血性中风、脊髓损伤、多发性硬化症、认知功能和疼痛。PD-1 信号通过驻留的小胶质细胞和浸润的外周免疫细胞抑制 CNS 免疫反应。值得注意的是，PD-1 也广泛表达于神经元中，通过下游 Src 同源性 2 结构域含有蛋白酪氨酸磷酸酶 1 和离子通道功能的调节来抑制神经元活性。深入了解 PD-1 信号在 CNS 中神经胶质细胞、神经元和外周免疫细胞之间的相互作用，将有助于阐明免疫调节、神经调节以及治疗脑部疾病的新策略。
