EP2 inhibition restores myeloid metabolism and reverses cognitive decline

Nonsteroidal anti-inflammatory drugs alleviate pain and inflammation by inhibiting the cyclooxygenase pathway. This pathway has various downstream effects, some of which are beneficial. Prostaglandin E(2) is a key downstream product in the cyclooxygenase pathway that modulates inflammation. A correlation between aging and increased expression of the prostaglandin E(2) receptor, EP2, has been associated with inflammatory processes, cognitive aging, angiogenesis, and tumorigenesis. Therefore, inhibition of EP2 could lead to therapeutic effects and be more selective than inhibiting cyclooxygenase-2. Studies suggest that inhibition of EP2 restores age-associated spatial memory deficits and synaptic proteins and impairs tumorigenesis. The data indicate that EP2 signaling is important in myeloid cell metabolism and support its candidacy as a therapeutic target.