TRP Channels: New Potential Therapeutic Approaches in CNS Neuropathies

Abstract

More than 30 different Transient Receptor Potential channels (TRP) have been identified in mammals and are grouped in 6 families. Members of these subunit families, specifically of the vanilloid TRP (TRPV), melastatin TRP (TRPM), ankyrin TRP (TRPA), polycystin TRP (TRPP) and canonical or classical TRP (TRPC) family, are considered relevant in central nervous system neurodegenerative diseases. In fact, TRP channels have received increased attention in recent years, since they are involved in a broad array of pathways and respond to different environmental stimuli. Preclinical research has identified TRPs involved in hereditary neuropathies as well as in a heterogeneous group of neuronal disorders. Moreover, changes in TRP channel expression and functionality have been associated to diabetic thermal hyperalgesia, painful neuropathies and headache. At the molecular level, TRPs are involved in a wide range of mechanisms regulating osmosis, thermal, stretch, chemical and sensory signaling, highlighting TRPs as potential targets for pharmacological intervention. The area of small molecule TRP agonists/antagonists drug development is moving rapidly. This review will evaluate current evidence that supports particular TRP channels as targets for novel drugs, summarizing the current perspectives for the therapeutic potential of TRP agonists and antagonists in the treatment of a wide range of neuropathies, along with potential adverse effects that may limit drug development.