Olivia Hoffman, Nicholas H Varvel, Avtar S Roopra, Ray Dingledine
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Neuroinflammation and Disease: Pathways and Opportunities.
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.
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.