Proteinase-activated receptors in the nervous system

Recent data point to important roles for proteinases and their cognate proteinase-activated receptors (PARs) in the ontogeny and pathophysiology of the nervous system. PARs are a family of G-protein-coupled receptors that can affect neural cell proliferation, morphology and physiology. PARs also have important roles in neuroinflammatory and degenerative diseases such as human immunodeficiency virus-associated dementia, Alzheimer's disease and pain. These receptors might also influence the pathogenesis of stroke and multiple sclerosis, conditions in which the blood-brain barrier is disrupted. The diversity of effects of PARs on neural function and their widespread distribution in the nervous system make them attractive therapeutic targets for neurological disorders. Here, we review the roles of PARs in the central and peripheral nervous systems during health and disease, with a focus on neuroinflammatory and degenerative disorders.