Current understanding of TRPM7 pharmacology and drug development for stroke
Abstract
Christine You Jin BAE, Hong-shuo SUN*
Departments of Surgery, Physiology, and Pharmacology, Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8
The initial excitement and countles 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.
Keywords: ion channels; TRPM7; cerebral ischemia; stroke; neuroprotection; recombinant tissue plasminogen activator (rt-PA); glutamate receptors
This work was supported by a Discovery Grant from Natural Sciences and Engineering Research Council of Canada to Dr Hong-Shuo SUN. Christine You Jin BAE is a recipient of Ontario Graduate Scholarship.
* To whom correspondence should be addressed.
E-mail hss.sun@utoronto.ca
Received 2012-04-04 Accepted 2012-06-12
Keywords:
Departments of Surgery, Physiology, and Pharmacology, Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada M5S 1A8
The initial excitement and countles 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.
Keywords: ion channels; TRPM7; cerebral ischemia; stroke; neuroprotection; recombinant tissue plasminogen activator (rt-PA); glutamate receptors
This work was supported by a Discovery Grant from Natural Sciences and Engineering Research Council of Canada to Dr Hong-Shuo SUN. Christine You Jin BAE is a recipient of Ontario Graduate Scholarship.
* To whom correspondence should be addressed.
E-mail hss.sun@utoronto.ca
Received 2012-04-04 Accepted 2012-06-12