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Transient receptor potential melastatin 2 channels in neurological disorders: Mechanisms and animal models

Joe Steinman1† Andrea Ovcjak1† Zhengwei Luo1,2† Xinyang Zhang1,2 Luiz Roberto Britto3 Jeffrey T. Henderson4 Hong-Shuo Sun1,2,4* Zhong-Ping Feng1*
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1 Departments of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
2 Departments of Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
3 Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Sao Paulo, Brazil
4 Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada
Advanced Neurology 2022, 1(1), 3
Submitted: 18 December 2021 | Accepted: 17 March 2022 | Published: 8 April 2022
© 2022 by the Authors. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( )

Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable ion channel implicated in neurodegenerative disorders and conditions. It is activated in response to reactive oxygen species (ROS) and thereby alters Ca2+ homeostasis and initiates pathways that lead to apoptosis and cell dysfunction. This review summarizes the current role of TRPM2 in neurological disorders, including Parkinson’s disease, Alzheimer’s disease, ischemia, traumatic brain injury, and depressive disorders (bipolar disease and depression). It describes the distribution and function of the TRPM2 channel across the brain and highlights common mechanisms between diseases. Specific animal and cell culture studies using TRPM2 inhibitors or genetic knockouts are discussed, including strategies to reduce the effect of ROS in disease through TRPM2 inhibition.

Transient receptor potential melastatin 2
Ion channel
Neurological disorders
Brain injury
Natural Sciences and Engineering Research Council of Canada
Canadian Institutes of Health Research

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Conflict of interest
The authors have no competing interest to declare.
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