Takeo Nakanishi; Mamoru Fukuchi · 2026 · Brain Sciences
Paper
Background/Objectives: Prostaglandin E2 (PGE2) is a known inflammatory mediator. It is produced by cyclooxygenase (COX)-1/2 during inflammation via four distinct G protein-coupled receptors (EP1–EP4). PGE2 is involved in the development of brain diseases induced by acute and chronic stresses, although the mechanisms regulating PGE2 concentration remain unclear. This review summarizes the mechanisms in relation to the activity of PGE2, focusing on membrane transporters in neuroinflammation and central nervous system (CNS) disorders. Methodology: A literature search was conducted using the PubMed database to evaluate the roles and dynamics of PGE2 in the central nervous system (CNS) under acute and chronic stress conditions. Results: PGE2 produced during inflammation acts via four receptors (EP1–EP4). These receptors mediate diverse and complex pathways in neurons and glial cells (microglia and astrocytes), influencing pathologies involving acute and chronic inflammation such as cerebral ischemia, Alzheimer’s disease, Parkinson’s disease, and neuropathic pain. EP1, EP2, and EP3 generally promote neurotoxicity, inflammation, and blood–brain barrier disruption, whereas EP4 predominantly exerts anti-inflammatory and neuroprotective effects. Furthermore, membrane transporters, particularly SLCO2A1 (also known as PGT) and MRP4 (encoded by ABCC4), regulate local PGE2 concentrations and facilitate its clearance across the blood–brain and blood–cerebrospinal fluid barriers. Understanding these transporters and receptors provides insights into controlling PGE2 dynamics in CNS diseases. Conclusions: Growing evidence indicates that membrane transporters play critical roles in regulating these levels in the brain, and elucidating the expression profiles of functional PG transporters may offer novel therapeutic strategies for refractory inflammation-based CNS diseases.
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