Role of TRPM2 in brain tumours and potential as a drug target
- 9 June 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Acta Pharmacologica Sinica
- Vol. 43 (4), 759-770
- https://doi.org/10.1038/s41401-021-00679-4
Abstract
Ion channels are ubiquitously expressed in almost all living cells, and are the third-largest category of drug targets, following enzymes and receptors. The transient receptor potential melastatin (TRPM) subfamily of ion channels are important to cell function and survival. Studies have shown upregulation of the TRPM family of ion channels in various brain tumours. Gliomas are the most prevalent form of primary malignant brain tumours with no effective treatment; thus, drug development is eagerly needed. TRPM2 is an essential ion channel for cell function and has important roles in oxidative stress and inflammation. In response to oxidative stress, ADP-ribose (ADPR) is produced, and in turn activates TRPM2 by binding to the NUDT9-H domain on the C-terminal. TRPM2 has been implicated in various cancers and is significantly upregulated in brain tumours. This article reviews the current understanding of TRPM2 in the context of brain tumours and overviews the effects of potential drug therapies targeting TRPM2 including hydrogen peroxide (H2O2), curcumin, docetaxel and selenium, paclitaxel and resveratrol, and botulinum toxin. It is long withstanding knowledge that gliomas are difficult to treat effectively, therefore investigating TRPM2 as a potential therapeutic target for brain tumours may be of considerable interest in the fields of ion channels and pharmacology.Keywords
This publication has 151 references indexed in Scilit:
- Transient Receptor Potential Melastatin 2 (TRPM2) ion channel is required for innate immunity againstListeria monocytogenesProceedings of the National Academy of Sciences of the United States of America, 2011
- Identification of Direct and Indirect Effectors of the Transient Receptor Potential Melastatin 2 (TRPM2) Cation Channel*Online Journal of Public Health Informatics, 2010
- Resveratrol attenuates the anticancer efficacy of paclitaxel in human breast cancer cells invitro and in vivoEuropean Journal of Cancer, 2010
- TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascadeProceedings of the National Academy of Sciences of the United States of America, 2009
- Modulation of TRPM2 by acidic pH and the underlying mechanisms for pH sensitivityThe Journal of general physiology, 2009
- Intracellular calcium activates TRPM2 and its alternative spliced isoformsProceedings of the National Academy of Sciences of the United States of America, 2009
- Identification of Pore Residues Engaged in Determining Divalent Cationic Permeation in Transient Receptor Potential Melastatin Subtype Channel 2Online Journal of Public Health Informatics, 2008
- Age‐related decreases in NAD(P)H and glutathione cause redox declines before ATP loss during glutamate treatment of hippocampal neuronsJournal of Neuroscience Research, 2008
- Inhibition of the transient receptor potential cation channel TRPM2 by 2‐aminoethoxydiphenyl borate (2‐APB)British Journal of Pharmacology, 2008
- Inhibition of TRPM2 cation channels by N‐(p‐amylcinnamoyl)anthranilic acidBritish Journal of Pharmacology, 2006