Page 78 - AN-1-1

Advanced Neurology

REVIEW ARTICLE
Transient receptor potential

melastatin 2 channels in neurological
disorders: Mechanisms and animal models

1,2
1†
1†
Joe Steinman , Andrea Ovcjak , Zhengwei Luo 1,2† , Xinyang Zhang ,
4
Luiz Roberto Britto , Jeffrey T. Henderson , Hong-Shuo Sun 1,2,4 *,
3
1
and Zhong-Ping Feng *
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

Abstract

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 Ca homeostasis and initiates
2+
pathways that lead to apoptosis and cell dysfunction. This review summarizes
† These authors contributed equally the current role of TRPM2 in neurological disorders, including Parkinson’s disease,
to this work. Alzheimer’s disease, ischemia, traumatic brain injury, and depressive disorders
*Corresponding authors: (bipolar disease and depression). It describes the distribution and function of the
Hong-Shuo Sun
(hss.sun@utoronto.ca) TRPM2 channel across the brain and highlights common mechanisms between
Zhong-Ping Feng diseases. Specific animal and cell culture studies using TRPM2 inhibitors or genetic
(zp.feng@utoronto.ca) knockouts are discussed, including strategies to reduce the effect of ROS in disease
Citation: Steinman J, Ovcjak A, through TRPM2 inhibition.
Luo Z, et al., 2022, Transient
receptor potential melastatin 2
channels in neurological disorders: Keywords: Transient receptor potential melastatin 2; Ion channel; Neurological disorders;
Mechanisms and animal models.
Adv Neuro, 1(1): 3. Brain injury; Stroke
https://doi.org/10.36922/an.v1i1.3
Received: December 18, 2021
Accepted: March 17, 2022 1. Introduction
Published Online: April 8, 2022 Understanding of the molecular mechanisms underlying cell damage in neurological
Copyright: © 2022 Author(s). diseases is improving; however, challenges remain in therapeutic development. In
This is an Open Access article Alzheimer’s disease (AD), therapies targeting amyloid or tau pathology have not been
distributed under the terms of the
[1]
Creative Commons Attribution successfully translated from animal studies (mice) to humans . Similarly, therapeutic
[2]
License, permitting distribution, options remain limited in ischemia and brain injury .
and reproduction in any medium,
provided the original work is There are a variety of reasons for poor clinical translation. Numerous independent and
properly cited. interrelated molecular mechanisms are altered during disease or injury. Consequently,
Publisher’s Note: AccScience targeting a single mechanism may not be sufficient to minimize tissue damage. For
Publishing remains neutral with example, in traumatic brain injury (TBI), microvascular remodeling and angiogenesis
regard to jurisdictional claims in [3]
published maps and institutional occur to restore blood flow . This process, however, occurs concurrently with gliosis,
affiliations. widespread neural degeneration, and axonal injury . Animal models, typically used
[4]

Volume 1 Issue 1 (2022) 1 https://doi.org/10.36922/an.v1i1.3