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Current understanding of TRPM7 pharmacology and drug development for stroke
Christine You Jin Bae1, Hong-shuo Sun
1Departments of Surgery, Physiology, and Pharmacology, Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Abstract:
The initial excitement and countless efforts to find a pharmacological agent that disrupts the excitotoxic pathway of ischemic neuronal death have only led to disappointing clinical trials. Currently, a thrombolytic agent called recombinant tissue plasminogen activator (rt-PA) is the only pharmacological treatment available for patients with acute ischemic stroke in most countries. Even though its efficacy has been confirmed repeatedly, rt-PA is considerably underused due to reasons including a short therapeutic window and repeated complications associated with its use. A search for alternative mechanisms that may operate dependently or independently with the well-established excitotoxic mechanism has led researchers to the discovery of newly described non-glutamate mechanisms. Among the latter, transient receptor potential melastatin 7 (TRPM7) is one of the important nonglutamate mechanisms in stroke, which has been evaluated in both in-vitro and in-vivo. In this review, we will discuss the current state of pharmacological treatments of ischemic stroke and provide evidence that TRPM7 is a promising therapeutic target of stroke.
Insights
Current treatments for ischemic stroke are limited. This review highlights Transient Receptor Potential Melastatin 7 (TRPM7) as a promising new therapeutic target for stroke, offering an alternative to existing therapies.
Area of Science:
- Neuroscience
- Pharmacology
- Biomedical Research
Background:
- Pharmacological treatments for ischemic stroke have yielded disappointing results.
- Recombinant tissue plasminogen activator (rt-PA) is the sole approved drug but has limitations like a narrow therapeutic window.
- Research is exploring non-glutamate pathways for novel stroke therapies.
Purpose of the Study:
- To review current pharmacological treatments for ischemic stroke.
- To present evidence supporting Transient Receptor Potential Melastatin 7 (TRPM7) as a viable therapeutic target.
- To discuss the role of TRPM7 in stroke pathophysiology.
Main Methods:
- Literature review of existing stroke treatments.
- Analysis of in-vitro and in-vivo studies on TRPM7.
- Evaluation of TRPM7's role in non-glutamate excitotoxic pathways.
Main Results:
- Existing excitotoxic pathway targets have shown limited clinical success.
- TRPM7 has been identified as a significant non-glutamate mechanism in stroke.
- TRPM7 has demonstrated potential in both in-vitro and in-vivo models.
Conclusions:
- TRPM7 represents a promising therapeutic target for ischemic stroke.
- Targeting TRPM7 may offer an alternative or complementary approach to current stroke treatments.
- Further research into TRPM7 modulation is warranted for clinical application.