Proteinase-Activated Receptors in The Nervous System: Physiological and Pathological Aspects

Proteinase-activated receptors (PARs), a family of four G protein-coupled receptors, are characterized by their unique activation mechanism which involves the proteolytic unmasking of a tethered ligand. To date, four PARs receptors have been discovered in human and mammals. All four members of the PARs family are expressed in the nervous system, where they have been shown to affect neural cell morphology, proliferation, and function. Furthermore, PARs play significant roles in degenerative and neuroinflammatory diseases, including Alzheimer’s disease, multiple sclerosis, HIV-associated dementia, and stroke. The widespread distribution of PARs in the nervous system and their potential roles in different disorders make them attractive therapeutic targets for neurological diseases.
In this review we summarize the roles of PARs in the central and peripheral nervous systems in the physiological setting as well as in pathological conditions.