Neuroinflammation and Disease: Pathways and Opportunities.

IF 13.1 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Olivia Hoffman, Nicholas H Varvel, Avtar S Roopra, Ray Dingledine
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引用次数: 0

Abstract

We explore three emerging molecular pathways driving neuroinflammation in chronic and acute brain diseases: the EP2 receptor for prostaglandin E2, the CCR2 receptor for chemokine CCL2, and JAK/STAT signaling. Inflammation is now recognized as a causative factor in neurodegenerative disorders, with neuroinflammation preceding symptom onset in Alzheimer's disease and likely heralding the onset of epilepsy and Parkinson's disease. The EP2 receptor modulates immune cell activation and exacerbates inflammatory responses, while CCR2 regulates peripheral immune cell recruitment to sites of brain inflammation. JAK/STAT pathways regulate neuronal and glial function across brain regions and can both amplify and resolve neuroinflammatory processes. These three signaling pathways converge at multiple nodes-immune cell recruitment, cytokine amplification, and transcriptional regulation-establishing feedforward loops that sustain pathology in chronic diseases. Understanding these mechanisms and their complex interactions provides opportunities for novel therapeutic interventions in neurological conditions characterized by inflammation, potentially leading to disease-modifying treatments.

神经炎症和疾病:途径和机会。
我们探索了慢性和急性脑疾病中驱动神经炎症的三种新兴分子途径:前列腺素E2的EP2受体、趋化因子CCL2的CCR2受体和JAK/STAT信号。炎症现在被认为是神经退行性疾病的一个致病因素,神经炎症在阿尔茨海默病的症状发作之前,可能预示着癫痫和帕金森病的发作。EP2受体调节免疫细胞激活并加剧炎症反应,而CCR2调节外周免疫细胞向脑炎症部位的募集。JAK/STAT通路调节大脑区域的神经元和神经胶质功能,可以放大和解决神经炎症过程。这三种信号通路汇聚在多个节点上——免疫细胞募集、细胞因子扩增和转录调节——建立前馈回路,维持慢性疾病的病理。了解这些机制及其复杂的相互作用为以炎症为特征的神经系统疾病的新型治疗干预提供了机会,可能导致疾病改善治疗。
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来源期刊
CiteScore
27.80
自引率
0.00%
发文量
53
期刊介绍: Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
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