title: Current understanding of TRPM7 pharmacology and drug development for stroke.
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.
authors: Departments of Surgery, Physiology, and Pharmacology, Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors: Christine You Jin
authors: CY
authors: Bae
authors: Hong-shuo
authors: HS
authors: Sun
mesh_terms: D000818:Animals; D055808:Drug Discovery / Q000379:methods; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D018696:Neuroprotective Agents / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases; D017470:Receptors, Glutamate / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015912:Thrombolytic Therapy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
chemical_list: D005343:Fibrinolytic Agents; D018696:Neuroprotective Agents; D017470:Receptors, Glutamate; D011994:Recombinant Proteins; D050053:TRPM Cation Channels; D017346:Protein Serine-Threonine Kinases; C486583:TRPM7 protein, human; D010959:Tissue Plasminogen Activator