scholarly journals Roles of TRP Channels in Neurological Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Rui Wang ◽  
Sheng Tu ◽  
Jianmin Zhang ◽  
Anwen Shao
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Receptor Potential ◽  
Physiological Processes ◽  
Neuroprotective Strategies ◽  
Transient Receptor ◽  
Physical And Chemical ◽  
The Brain

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.

scholarly journals TRPM2 in the Brain: Role in Health and Disease

Cells ◽  
2018 ◽  
Vol 7 (7) ◽  
pp. 82 ◽  
Author(s):  
Giulia Sita ◽  
Patrizia Hrelia ◽  
Agnese Graziosi ◽  
Gloria Ravegnini ◽  
Fabiana Morroni
Keyword(s):  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Cell Functions ◽  
Neuroprotective Strategies ◽  
Health And Disease ◽  
Future Potential ◽  
Transient Receptor ◽  
Multiple Signaling ◽  
The Brain

Transient receptor potential (TRP) proteins have been implicated in several cell functions as non-selective cation channels, with about 30 different mammalian TRP channels having been recognized. Among them, TRP-melastatin 2 (TRPM2) is particularly involved in the response to oxidative stress and inflammation, while its activity depends on the presence of intracellular calcium (Ca2+). TRPM2 is involved in several physiological and pathological processes in the brain through the modulation of multiple signaling pathways. The aim of the present review is to provide a brief summary of the current insights of TRPM2 role in health and disease to focalize our attention on future potential neuroprotective strategies.

scholarly journals The Transient Receptor Potential Melastatin 7 (TRPM7) Inhibitors Suppress Seizure-Induced Neuron Death by Inhibiting Zinc Neurotoxicity

2020 ◽  
Vol 21 (21) ◽  
pp. 7897
Author(s):  
Jeong Hyun Jeong ◽  
Song Hee Lee ◽  
A Ra Kho ◽  
Dae Ki Hong ◽  
Dong Hyeon Kang ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Therapeutic Potential ◽  
Divalent Cations ◽  
Neurological Diseases ◽  
Receptor Potential ◽  
Neuron Death ◽  
Intracellular Zinc ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
Induced Neuron

Transient receptor potential melastatin 7 (TRPM7) is an ion channel that mediates monovalent cations out of cells, as well as the entry of divalent cations, such as zinc, magnesium, and calcium, into the cell. It has been reported that inhibitors of TRPM7 are neuroprotective in various neurological diseases. Previous studies in our lab suggested that seizure-induced neuronal death may be caused by the excessive release of vesicular zinc and the subsequent accumulation of zinc in the neurons. However, no studies have evaluated the effects of carvacrol and 2-aminoethoxydiphenyl borate (2-APB), both inhibitors of TRPM7, on the accumulation of intracellular zinc in dying neurons following seizure. Here, we investigated the therapeutic efficacy of carvacrol and 2-APB against pilocarpine-induced seizure. Carvacrol (50 mg/kg) was injected once per day for 3 or 7 days after seizure. 2-APB (2 mg/kg) was also injected once per day for 3 days after seizure. We found that inhibitors of TRPM7 reduced seizure-induced TRPM7 overexpression, intracellular zinc accumulation, and reactive oxygen species production. Moreover, there was a suppression of oxidative stress, glial activation, and the blood–brain barrier breakdown. In addition, inhibitors of TRPM7 remarkably decreased apoptotic neuron death following seizure. Taken together, the present study demonstrates that TRPM7-mediated zinc translocation is involved in neuron death after seizure. The present study suggests that inhibitors of TRPM7 may have high therapeutic potential to reduce seizure-induced neuron death.

Transient Receptor Potential (TRP) Channels in the Brain: the Good and the Ugly

2012 ◽  
Vol 20 (3) ◽  
pp. 343-355 ◽  
Author(s):  
Bernd Nilius
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Sensory Function ◽  
Short Paper ◽  
The Novel ◽  
Cellular Functions ◽  
Transient Receptor ◽  
The Brain

The ‘transient receptor potential’ (TRP) multigene family encodes sixspan membrane proteins that function as ion channels in mostly tetrameric structures. Members of this family are conserved from yeast, worm, fly to invertebrate, vertebrate and man. These channels have been stigmatized to function only as cell sensors occupied by sensory function. It turns out that TRP channels fulfil a plethora of cellular functions, including non-sensory functions in our brain. This short paper will highlight the advent of novel ion channels in the brain serving different functions and being significantly involved in the genesis of multiple diseases. We will certainly witness a plethora of the novel roles of this protein family in physiological and pathophysiological functions in our central nervous system.

scholarly journals TRPM8 Channels and Dry Eye

2018 ◽  
Vol 11 (4) ◽  
pp. 125 ◽  
Author(s):  
Jee Yang ◽  
Edward Wei ◽  
Seong Kim ◽  
Kyung Yoon
Keyword(s):  
Foreign Body ◽  
Dry Eye ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Eye Disease ◽  
Chemical Irritation ◽  
Body Discomfort ◽  
Transient Receptor ◽  
The Brain

Transient receptor potential (TRP) channels transduce signals of chemical irritation and temperature change from the ocular surface to the brain. Dry eye disease (DED) is a multifactorial disorder wherein the eyes react to trivial stimuli with abnormal sensations, such as dryness, blurring, presence of foreign body, discomfort, irritation, and pain. There is increasing evidence of TRP channel dysfunction (i.e., TRPV1 and TRPM8) in DED pathophysiology. Here, we review some of this literature and discuss one strategy on how to manage DED using a TRPM8 agonist.

scholarly journals Structural mechanisms of transient receptor potential ion channels

2020 ◽  
Vol 152 (3) ◽  
Author(s):  
Erhu Cao
Keyword(s):  
Ion Channels ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Wide Range ◽  
Human Disorders ◽  
Transient Receptor ◽  
Voltage Gated Ion Channels ◽  
Structural Mechanisms ◽  
Physical And Chemical

Transient receptor potential (TRP) ion channels are evolutionarily ancient sensory proteins that detect and integrate a wide range of physical and chemical stimuli. TRP channels are fundamental for numerous biological processes and are therefore associated with a multitude of inherited and acquired human disorders. In contrast to many other major ion channel families, high-resolution structures of TRP channels were not available before 2013. Remarkably, however, the subsequent “resolution revolution” in cryo-EM has led to an explosion of TRP structures in the last few years. These structures have confirmed that TRP channels assemble as tetramers and resemble voltage-gated ion channels in their overall architecture. But beyond the relatively conserved transmembrane core embedded within the lipid bilayer, each TRP subtype appears to be endowed with a unique set of soluble domains that may confer diverse regulatory mechanisms. Importantly, TRP channel TR structures have revealed sites and mechanisms of action of numerous synthetic and natural compounds, as well as those for endogenous ligands such as lipids, Ca2+, and calmodulin. Here, I discuss these recent findings with a particular focus on the conserved transmembrane region and how these structures may help to rationally target this important class of ion channels for the treatment of numerous human conditions.

scholarly journals Structure, function, and mechanism of action of the vanilloid TRPV1 receptor

2020 ◽  
Vol 74 ◽  
pp. 481-488
Author(s):  
Paweł Siudem ◽  
Katarzyna Paradowska
Keyword(s):  
Mechanism Of Action ◽  
Transient Receptor Potential ◽  
Therapeutic Potential ◽  
Sensory Nerve ◽  
Receptor Potential ◽  
Nerve Fibers ◽  
Trpv1 Receptor ◽  
Transient Receptor ◽  
Irritable Bowel ◽  
Physical And Chemical

The TRPV1 receptor (transient receptor potential cation channel subfamily V member 1) is a non-selective cationic channel activated by vanilloids like capsaicin. Therefore, TRPV1 is also called a capsaicin’s receptor, which is a spicy substance found in chili peppers. The receptor is located in sensory nerve fibers and non-neuronal cells, for example in vascular endothelial and smooth muscle cells. It is thought to act as an integrator of various physical and chemical stimuli that provide heat and pain. The activation of the TRPV1 may affect at various physiological functions like release inflammatory mediators, gastrointestinal motility and temperature regulation. Numerous studies in recent years show TRPV1 plays an important role in physiology and development of pathological conditions of gastrointestinal, cardiovascular and respiratory system. These receptors are widely studied as a gripping point for new painkillers, but there are also data indicating their potential involvement in the pathomechanism of various diseases, e.g. epilepsy. TRPV1 targeting may be useful not only in paintreatment but also urinary incontinence, chronic cough or irritable bowel syndrome. The need for further investigation of the therapeutic potential of TRPV1 antagonists indicates the lack of effective drugs to treat many of these conditions. The purpose of this article is to collect and summarize knowledge about the TRPV1 receptor, its structure and mechanism of action.

scholarly journals Thermosensory Transient Receptor Potential Ion Channels and Asthma

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 816
Author(s):  
Oxana Yu. Kytikova ◽  
Tatyana P. Novgorodtseva ◽  
Yulia K. Denisenko ◽  
Denis E. Naumov ◽  
Tatyana A. Gvozdenko ◽  
...  
Keyword(s):  
Ion Channels ◽  
Low Temperatures ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Anthropogenic Factors ◽  
Genes Encoding ◽  
Transient Receptor ◽  
High And Low Temperatures ◽  
Physical And Chemical

Asthma is a widespread chronic disease of the bronchopulmonary system with a heterogeneous course due to the complex etiopathogenesis. Natural-climatic and anthropogenic factors play an important role in the development and progression of this pathology. The reception of physical and chemical environmental stimuli and the regulation of body temperature are mediated by thermosensory channels, members of a subfamily of transient receptor potential (TRP) ion channels. It has been found that genes encoding vanilloid, ankyrin, and melastatin TRP channels are involved in the development of some asthma phenotypes and in the formation of exacerbations of this pathology. The review summarizes modern views on the role of high and low temperatures in airway inflammation in asthma. The participation of thermosensory TRP channels (vanilloid, ankyrin, and melastatin TRP channels) in the reaction to high and low temperatures and air humidity as well as in the formation of bronchial hyperreactivity and respiratory symptoms accompanying asthma is described. The genetic aspects of the functioning of thermosensory TRP channels are discussed. It is shown that new methods of treatment of asthma exacerbations caused by the influence of temperature and humidity should be based on the regulation of channel activity.

scholarly journals Cannabidiol as a Potential Treatment for Anxiety and Mood Disorders: Molecular Targets and Epigenetic Insights from Preclinical Research

2021 ◽  
Vol 22 (4) ◽  
pp. 1863
Author(s):  
Philippe A. Melas ◽  
Maria Scherma ◽  
Walter Fratta ◽  
Carlo Cifani ◽  
Paola Fadda
Keyword(s):  
Mood Disorders ◽  
Cannabinoid Receptors ◽  
Transient Receptor Potential ◽  
Therapeutic Potential ◽  
Molecular Targets ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Preclinical Research ◽  
Neuropsychiatric Diseases ◽  
Transient Receptor

Cannabidiol (CBD) is the most abundant non-psychoactive component of cannabis; it displays a very low affinity for cannabinoid receptors, facilitates endocannabinoid signaling by inhibiting the hydrolysis of anandamide, and stimulates both transient receptor potential vanilloid 1 and 2 and serotonin type 1A receptors. Since CBD interacts with a wide variety of molecular targets in the brain, its therapeutic potential has been investigated in a number of neuropsychiatric diseases, including anxiety and mood disorders. Specifically, CBD has received growing attention due to its anxiolytic and antidepressant properties. As a consequence, and given its safety profile, CBD is considered a promising new agent in the treatment of anxiety and mood disorders. However, the exact molecular mechanism of action of CBD still remains unknown. In the present preclinical review, we provide a summary of animal-based studies that support the use of CBD as an anxiolytic- and antidepressant-like compound. Next, we describe neuropharmacological evidence that links the molecular pharmacology of CBD to its behavioral effects. Finally, by taking into consideration the effects of CBD on DNA methylation, histone modifications, and microRNAs, we elaborate on the putative role of epigenetic mechanisms in mediating CBD’s therapeutic outcomes.

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