Abstract
Transient receptor potential (TRP) proteins consist of a superfamily of cation channels that have been involved in diverse physiological processes in the brain as well as in the pathogenesis of neurological disease. TRP channels are widely expressed in the brain, including neurons and glial cells, as well as in the cerebral vascular endothelium and smooth muscle. Members of this channel superfamily show a wide variety of mechanisms ranging from ligand binding to voltage, physical, and chemical stimuli, implying the promising therapeutic potential of TRP in neurological diseases. In this review, we focus on the physiological functions of TRP channels in the brain and the pathological roles in neurological disorders to explore future potential neuroprotective strategies.
Highlights
The transient receptor potential (TRP) channels are a superfamily of cation channels that play critical roles in the responses to diverse environmental changes and stimuli
Studies have shown that TRPM2 and TRPM7 gating lies downstream of several signaling pathways in response to oxidative stress induced by cerebral ischemia and reperfusion injury, which is considered to be an important event leading to neuronal death
A recent work in animals and humans has increased the understanding of TRPs in the brain with their widespread distribution and varying functional roles
Summary
The transient receptor potential (TRP) channels are a superfamily of cation channels that play critical roles in the responses to diverse environmental changes and stimuli. Intracellular N- and C-termini have less homology between subfamilies, and they are variable in length and sequence with a variety of domains and motifs These diverse cytosolic domains play a role in channel assembly, activation, and regulation, which is one of the most fascinating structural aspects of TRP channels [5]. The activation of TRP channels by various stimuli and ligand binding contributes to changes in several monovalent and divalent cations, especially calcium These contributions are important for several physiological functions, including sensitivity to stimuli (i.e., pheromone signaling cascades, thermosensation, and mechanosensation), ion homeostasis (i.e., calcium and magnesium reabsorption and osmoregulation), and motility (i.e., muscle contraction and vasomotor control) [2]. Single-cell transcriptomic data suggests that TRPC, TRPV and TRPM channels can be found in mouse oligodendrocyte lineages, though their functions, to date, largely remain unknown [48]. It is reported that TRPV4 and TRPM4 are detected differently in endothelial cells and smooth muscle cells, contributing to myogenic vasoconstriction of cerebral arteries via a Ca2+ influx induced by various factors [53, 54]
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