Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Mar 4:9:611773.
doi: 10.3389/fcell.2021.611773. eCollection 2021.

Functional Importance of Transient Receptor Potential (TRP) Channels in Neurological Disorders

Kihwan Lee  1 , Youn Yi Jo  2 , Gehoon Chung  3 , Jung Hoon Jung  4 , Yong Ho Kim  1 , Chul-Kyu Park  1
Affiliations
Review

Functional Importance of Transient Receptor Potential (TRP) Channels in Neurological Disorders

Kihwan Lee et al. Front Cell Dev Biol. .

Abstract

Transient receptor potential (TRP) channels are transmembrane protein complexes that play important roles in the physiology and pathophysiology of both the central nervous system (CNS) and the peripheral nerve system (PNS). TRP channels function as non-selective cation channels that are activated by several chemical, mechanical, and thermal stimuli as well as by pH, osmolarity, and several endogenous or exogenous ligands, second messengers, and signaling molecules. On the pathophysiological side, these channels have been shown to play essential roles in the reproductive system, kidney, pancreas, lung, bone, intestine, as well as in neuropathic pain in both the CNS and PNS. In this context, TRP channels have been implicated in several neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and epilepsy. Herein, we focus on the latest involvement of TRP channels, with a special emphasis on the recently identified functional roles of TRP channels in neurological disorders related to the disruption in calcium ion homeostasis.

Keywords: Alzheimer’s disease; Huntington’s disease; Parkinson’s disease; TRP channels; amyotrophic lateral sclerosis; calcium homeostasis; epilepsy; neurological disorders.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic of the molecular mechanism of TRP channel-mediated pathogenesis of neurological disorders: (A) Alzheimer’s disease, (B) Parkinson’s disease, (C) Huntington’s disease, (D) Amyotrophic lateral sclerosis, and (E) epilepsy. In the figure, red arrows represent increase or up-regulation; green arrows, decrease or down-regulation; red thick bar, inhibition of the signaling pathway; and black arrows, activation of the signaling pathway. Ion channels involved in each of the neurological disorders and their transporting ions, channel agonists, and antagonists are also shown in the figure. Abbreviations: BDNF, brain-derived neurotrophic factor; ROS, reactive oxygen species; Aβ, beta-amyloid; PPAR, peroxisome proliferator-activated receptor gamma; AMPK, 5′ adenosine monophosphate-activated protein kinase; mTOR, mechanistic target of rapamycin; NMDAR, N-methyl-D-aspartate receptor; NAADP, Nicotinic acid adenine dinucleotide phosphate; PI(3,4)P2, phosphatidylinositol (3,4)-bisphosphate; PD, Parkinson’s disease; ER, endoplasmic reticulum; GABA, gamma-aminobutyric acid; DA, dopamine; ALS/FTD, amyotrophic lateral sclerosis patients with frontotemporal dementia; L-BMAA, L-beta-methylamino-L-alanine; IL, interleukin; TNF-α, tumor necrosis factor alpha; CPZ, capsazepine; IRTX, 5′-Iodoresiniferatoxin; KA, kainic acid; pPKCα, phospho-protein kinase C alpha; pERK1/2, phospho-extracellular signal-regulated kinase 1/2.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aarts M., Iihara K., Wei W. L., Xiong Z. G., Arundine M., Cerwinski W., et al. (2003). A key role for TRPM7 channels in anoxic neuronal death. Cell 115 863–877. 10.1016/s0092-8674(03)01017-1 - DOI - PubMed
    1. Aarts M. M., Tymianski M. (2005). TRsPMs and neuronal cell death. Pflugers Arch. 451 243–249. - PubMed
    1. Abbott A. C., Calderon Toledo C., Aranguiz F. C., Inestrosa N. C., Varela-Nallar L. (2013). Tetrahydrohyperforin increases adult hippocampal neurogenesis in wild-type and APPswe/PS1DeltaE9 mice. J. Alzheimers Dis. 34 873–885. 10.3233/jad-121714 - DOI - PubMed
    1. Adhya P., Sharma S. S. (2019). Redox TRPs in diabetes and diabetic complications: mechanisms and pharmacological modulation. Pharmacol. Res. 146:104271. 10.1016/j.phrs.2019.104271 - DOI - PubMed
    1. Balleza-Tapia H., Crux S., Andrade-Talavera Y., Dolz-Gaiton P., Papadia D., Chen G., et al. (2018). TrpV1 receptor activation rescues neuronal function and network gamma oscillations from Abeta-induced impairment in mouse hippocampus in vitro. Elife 7:e37703. - PMC - PubMed

LinkOut - more resources