Table 3.
Potential J2 prostaglandin therapeutic targets.
| Target | Drugs | Effects | References |
|---|---|---|---|
| Cycloxygenases (COXs) | NSAIDS | COX inhibitors. Prevent/diminish neuroinflammation. Inhibit synthesis of all PGs. Exhibit cardiovascular, gastrointestinal and other side effects. | Iadecola and Gorelick, 2005; Rainsford, 2007; Ng and Chan, 2010 |
| Monoacyl-glycerol lipase (MAGL) | JZL184 | MAGL selective and irreversible inhibitor. Prevents/diminishes neuroinflammation. Inhibits synthesis of all PGs in the brain. No detectable gastrointestinal side effects. | Nomura et al., 2011; Legg, 2011 |
| H-PGDS | HQL-79 | H-PGDS inhibitor. Prevents demyelination, astroglyosis and spasticity in the twitcher mouse. Potential for treating Krabbe disease. | Mohri et al., 2006; Bosetti, 2007 |
| DP1 | Agonists | Effective against stroke. | Ahmad et al., 2010 |
| Antagonists | Treat ALS, Krabbe disease and pain. | Mohri et al., 2006; Di Giorgio et al., 2008; Jones et al., 2009; de Boer et al., 2014; | |
| DP2 | Antagonists | Effective anti-inflammatory drugs (for asthma and allergies). Potential for treating neurodegenerative diseases and pain. | Jones et al., 2009; Norman, 2014 |
| PPARy | Agonists | Effective against stroke, TBI, spinal cord injury, multiple sclerosis, AD, PD. | Combs et al., 2000; Diab et al., 2002; Kapadia et al., 2008; Nolan et al., 2013 |
| Prostaglandin TA Transporter (PGT) | T26A | Highly selective PGT competitive inhibitor. Prolongs prostaglandin half-life. | Chi et al., 2011 |
| Michael addition | PAPCAP27 | Increases intracellular cAMP. Protective for stroke, PD, HD and TBI. Prevents PGJ2-induced neurodamage in vitro and in vivo (PD model). | Reglodi et al., 2004; Metcalfe et al., 2012; Shivers et al., 2014 |
| Lipocardium | Negatively charged liposomes to deliver PGA2 to activated arterial wall lining cells to reduce atherosclerosis. | Homem de Bittencourt et al., 2007 |