Institute for Neuro-Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Ft. Lauderdale, FL 33328, USA.
Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Ft. Lauderdale, FL 33328, USA.
Cells. 2024 Mar 14;13(6):511. doi: 10.3390/cells13060511.
Neuroinflammatory and neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions of these disease pathogeneses is currently not clearly understood. These disorders show dysregulated neuroimmune and inflammatory responses, including activation of neurons, glial cells, and neurovascular unit damage associated with excessive release of proinflammatory cytokines, chemokines, neurotoxic mediators, and infiltration of peripheral immune cells into the brain, as well as entry of inflammatory mediators through damaged neurovascular endothelial cells, blood-brain barrier and tight junction proteins. Activation of glial cells and immune cells leads to the release of many inflammatory and neurotoxic molecules that cause neuroinflammation and neurodegeneration. Gulf War Illness (GWI) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic disorders that are also associated with neuroimmune dysfunctions. Currently, there are no effective disease-modifying therapeutic options available for these diseases. Human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, microglia, endothelial cells and pericytes are currently used for many disease models for drug discovery. This review highlights certain recent trends in neuroinflammatory responses and iPSC-derived brain cell applications in neuroinflammatory disorders.
神经炎症和神经退行性疾病包括阿尔茨海默病（AD）、帕金森病（PD）、创伤性脑损伤（TBI）和肌萎缩侧索硬化症（ALS）是慢性重大健康疾病。这些疾病发病机制中的神经免疫功能障碍的确切机制目前尚不清楚。这些疾病表现出失调的神经免疫和炎症反应，包括神经元、神经胶质细胞和神经血管单元的激活，以及与促炎细胞因子、趋化因子、神经毒性介质的过度释放相关的损伤，外周免疫细胞浸润到大脑中，以及炎症介质通过受损的神经血管内皮细胞、血脑屏障和紧密连接蛋白进入。神经胶质细胞和免疫细胞的激活导致许多炎症和神经毒性分子的释放，从而导致神经炎症和神经退行性变。海湾战争病（GWI）和肌痛性脑脊髓炎/慢性疲劳综合征（ME/CFS）也是与神经免疫功能障碍相关的慢性疾病。目前，这些疾病没有有效的疾病修饰治疗选择。人诱导多能干细胞（iPSC）衍生的神经元、星形胶质细胞、小胶质细胞、内皮细胞和周细胞目前用于许多疾病模型的药物发现。这篇综述强调了神经炎症反应和 iPSC 衍生脑细胞在神经炎症性疾病中的某些最新趋势。
