PARing down EAE

An excess of proteinase receptors in the brain aggravates demyelination in multiple sclerosis (MS), suggest Noorbakhsh and colleagues on page 425. Mice lacking proteinase-activated receptor-2 (PAR₂), they show, are protected from the brain damage characteristic of experimental autoimmune encephalomyelitis (EAE), a model of MS.

PAR₂, a G protein–coupled receptor activated by trypsin-like serine proteases, is best known as the primary pain receptor in the peripheral nervous system. But this receptor is also expressed on smooth muscle cells in the gut, where it stimulates muscle contraction, and on neurons and glial cells in the brain, where it is proposed to promote cell growth and survival.

This versatile receptor can also help promote inflammation. Indeed, activation of PAR₂ on skin cells triggers the production of inflammatory cytokines,...