Neuroscience,CNS disorders, Protease-activated receptor 2 (PAR2),neuroprotection, inflammation, EAE.

Brain disorders are high on the World Health Organization's agenda with recent reports highlighting the economic burden of mental and neurological disorders in Europe being at an estimated cost of over €400 billion p.a.^1,2. Hence novel targets for the treatment of these disorders are required and there has been increasing evidence in recent years that proteinase-activated receptor 2 (PAR2) may be a credible target.  PAR2 belongs to a novel family of G-protein coupled receptors (GPCR) that have received significant attention due to their proposed protective role in various inflammation-related CNS diseases including HIV dementia and Alzheimer's disease³.  However, determining the therapeutic potential of PAR2 in CNS disorders has been hindered due to the poor bioavailability and stability of current pharmacological tools⁵ as well as their inability to cross the blood brain barrier (BBB). To overcome these issues, novel PAR2 activators with high potency and good stability have been developed.  Our recent work has revealed that PAR2 activators are good candidates with which to examine the therapeutic potential of PAR2 in CNS disorders^3-5.  Indeed we have novel data indicating that recently developed brain permeable PAR2 activators are neuroprotective in in vitro models of neurotoxicity as we'll as reducing clinical scores in animal models of brain inflammation. 

In vivo models of CNS disorders, ELISA, FACS, immunohistochemistry, qPCR & western blotting.

1.      Nutt  & Goodwin (2011). Eur Neuropsychopharmacol 21: 495-499.

2.      Wittchen et al., (2011) Eur Neuropsychopharmacol 21: 655-679.

3.      Greenwood & Bushell (2010). J. Neurochem. 113:1471-80.

4.      Gan et al., (2011)  Brit. J. Pharmacol 163: 984-994.