The emergence of proteinase-activated receptor-2 as a novel target for the treatment of inflammation-related CNS disorders

The signalling molecules that are involved in inflammatory pathways are now thought to play a part in many disorders of the central nervous system (CNS). In common with peripheral chronic inflammatory diseases such a rheumatoid arthritis and ulcerative colitis, evidence now exists for the involvement of inflammatory cytokines, for example tumour necrosis factor (TNF) and interleukins (IL), in neurological disorders. A common factor observed with the up-regulation of these cytokines in peripheral inflammatory diseases, is the increased expression of the proteinase-activated receptor (PAR) subtype PAR-2. Indeed, recent evidence suggests that targeting PAR-2 helps reduce joint swelling observed in animal models of arthritis. So could targeting this receptor prove to be useful in treating those CNS disorders where inflammatory processes are thought to play an intrinsic role? The aim of this review is to summarize the emerging data regarding the role of PAR-2 in neuroinflammation and ischaemic injury and discuss its potential as an exciting new target for the prevention and/or treatment of CNS disorders.