TRPM2 in ischemic stroke: Structure, molecular mechanisms, and drug intervention

Ischemic stroke has a high lethality rate worldwide, and novel treatments are limited. Calcium overload is considered to be one of the mechanisms of cerebral ischemia. Transient receptor potential melastatin 2 (TRPM2) is a reactive oxygen species (ROS)-sensitive calcium channel. Cerebral ischemia-induced TRPM2 activation triggers abnormal intracellular Ca2+ accumulation and cell death, which in turn causes irreversible brain damage. Thus, TRPM2 has emerged as a new therapeutic target for ischemic stroke. This review provides data on the expression, structure, and function of TRPM2 and illustrates its cellular and molecular mechanisms in ischemic stroke. Natural and synthetic TRPM2 inhibitors (both specific and nonspecific) are also summarized. The three-dimensional protein structure of TRPM2 has been identified, and we speculate that molecular simulation techniques will be essential for developing new drugs that block TRPM2 channels. These insights about TRPM2 may be the key to find potent therapeutic approaches for the treatment of ischemic stroke.

Automated summary

Ischemic stroke has a high lethality rate globally, with calcium overload being one of the mechanisms of cerebral ischemia. TRPM2 activation in cerebral ischemia leads to abnormal intracellular Ca2+ accumulation and cell death, highlighting its potential as a therapeutic target. Insights into TRPM2's expression, structure, function, and inhibitors provide avenues for developing new drugs and potent therapeutic approaches for treating ischemic stroke.