TRPM2: a candidate therapeutic target for treating neurological diseases

Abstract Transient receptor potentialmelastatin 2 ( TRPM2) is a calcium (Ca 2+ )-permeable non-selective cation channel belonging to the TRP ion channel family. Oxidative stress-induced TRPM2activation provokes aberrant intracellular Ca 2+ accumulation and cell death in a variety of cell types, including neurons. Aberrant TRPM2function has been implicated in several neurological disordersincluding ischemia/ stroke, Alzheimer’s disease, neuropathic pain, Parkinson’s disease and bipolar disorder. In addition to research identifying a role for TRPM2in disease, progress has been made in the identification of physiological functions of TRPM2in the brain, including recent evidence that TRPM2is necessary for the induction of N-methyl- D -aspartate (NMDA) receptor-dependent long-term depression, an important form of synaptic plasticityat glutamate synapses. Here, we summarize recent evidence on the role of TRPM2in the central nervous system (CNS) in health and disease and discuss the potential therapeutic implications of targeting TRPM2. Collectively, these studies suggest that TRPM2represents a prospective novel therapeutic target for neurological disorders.