Prostaglandin J₂

Prostaglandin J₂ (PGJ₂) is a metabolite of PGD₂ (Item No. 12010) and an agonist of the prostaglandin D₂ (PGD₂) receptor subtypes DP₁ and DP₂/CRTH.^1,2 It is formed from PGD₂ by spontaneous dehydration.³ PGJ₂ binds to DP₁ and DP₂/CRTH receptors (K_is = 0.9 and 6.6 nM, respectively) and either increases or inhibits the production of cAMP (EC₅₀s = 1.2 and 13.1 nM, respectively, in HEK293 cells expressing the human receptors).^1,2 PGJ₂ is neurotoxic and induces apoptosis, oxidative stress, and the accumulation of ubiquitinated proteins in the brain.⁴ It promotes the cleavage of amyloid precursor protein (APP) by α- and β-secretase in primary rat cerebral cortical neurons when used at a concentration of 10 µM.³ The levels of PGJ₂ increase in the brain after stroke or traumatic brain injury (TBI) in rodents and it accumulates in the spinal cord of patients with sporadic amyotrophic lateral sclerosis (ALS).

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2. Sawyer, N., Cauchon, E., Chateauneuf, A., et al. Molecular pharmacology of the human prostaglandin D₂ receptor, CRTH2. Br. J. Pharmacol. 137, 1163-1172 (2002).

3. Jean-Louis, T., Rockwell, P., and Figueiredo-Pereira, M.E. Prostaglandin J₂ promotes O-GlcNAcylation raising APP processing by α- and β-secretases: Relevance to Alzheimer’s disease. Neurobiol. Aging 62, 130-145 (2018).

4. Figueiredo-Pereira, M.E., Corwin, C., and Babich, J. Prostaglandin J₂: A potential target for halting inflammation-induced neurodegeneration. Ann. N. Y. Acad. Sci. 1363(1), 125-137 (2016).

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Corwin, C., Nikolopoulou, A., Pan, A.L., et al. Prostaglandin D₂/J₂ signaling pathway in a rat model of neuroinflammation displaying progressive parkinsonian-like pathology: Potential novel therapeutic targets. J. Neuroinflammation 15(1), 272 (2018).

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Schröder, R., Xue, L., Konya, V., et al. PGH₁, the precursor for the anti-inflammatory prostaglandins of the 1-series, is a potent activator of the pro-inflammatory receptor CRTH2/DP₂. PLoS One 7(3), e33329 (2012).