TRPM2: a candidate therapeutic target for treating neurological diseases

Jillian Corinne Belrose,Michael Frederick Jackson

doi:10.1038/aps.2018.31

Abstract

Transient receptor potential melastatin 2 (TRPM2) is a calcium (Ca2+)-permeable non-selective cation channel belonging to the TRP ion channel family. Oxidative stress-induced TRPM2 activation provokes aberrant intracellular Ca2+ accumulation and cell death in a variety of cell types, including neurons. Aberrant TRPM2 function has been implicated in several neurological disorders including ischemia/stroke, Alzheimer's disease, neuropathic pain, Parkinson's disease and bipolar disorder. In addition to research identifying a role for TRPM2 in disease, progress has been made in the identification of physiological functions of TRPM2 in the brain, including recent evidence that TRPM2 is necessary for the induction of N-methyl-D-aspartate (NMDA) receptor-dependent long-term depression, an important form of synaptic plasticity at glutamate synapses. Here, we summarize recent evidence on the role of TRPM2 in the central nervous system (CNS) in health and disease and discuss the potential therapeutic implications of targeting TRPM2. Collectively, these studies suggest that TRPM2 represents a prospective novel therapeutic target for neurological disorders.

Highlights

Transient receptor potential melastatin 2 (TRPM2) is a calcium (Ca2+)-permeable non-selective cation channel first cloned and described in 1998[1]
Aberrant TRPM2 function has been implicated in various neurological disorders, which is not surprising when one considers that TRPM2 expression levels are highest in the central nervous system (CNS), channel activation occurs in response to oxidative and nitrosative stress, and channel-mediated Ca2+ entry has been linked to cell death
Summary As highlighted in this review, numerous studies have established the important contribution of TRPM2 to a wide variety of CNS diseases, including ischemia/stroke, Alzheimer’s disease, neuropathic pain, bipolar disorder, and Parkinson’s disease

Summary

Introduction

Transient receptor potential melastatin 2 (TRPM2) is a calcium (Ca2+)-permeable non-selective cation channel first cloned and described in 1998[1]. These findings suggest that the mitochondrial production of ADPR is critical for the activation of TRPM2 channels in response to oxidative stress. In addition to ADPR, several studies have suggested that NAD+ is capable of activating TRPM2 channels[23, 31, 32]; this finding has not been consistently reproduced in the literature[8, 16].

Results

Conclusion