TRPM7 in cerebral ischemia and potential target for drug development in stroke

被引:45
作者
Bae, Christine You-jin [2 ]
Sun, Hong-shuo [1 ,2 ,3 ,4 ]
机构
[1] Univ Toronto, Fac Med, Dept Surg, Toronto, ON M5S 1A8, Canada
[2] Univ Toronto, Fac Med, Dept Physiol, Toronto, ON M5S 1A8, Canada
[3] Univ Toronto, Fac Med, Dept Pharmacol, Toronto, ON M5S 1A8, Canada
[4] Univ Toronto, Fac Med, Inst Med Sci, Toronto, ON M5S 1A8, Canada
关键词
ion channels; TRP; TRPM7; cerebral ischemia; stroke; in vivo test; siRNA; neuroprotection; SMOOTH-MUSCLE-CELLS; CHANNEL KINASES TRPM6; SENSING ION CHANNELS; CATION CHANNEL; NEURONAL DEATH; HIPPOCAMPAL-NEURONS; MOLECULAR DETERMINANTS; REPERFUSION INJURY; DIVALENT-CATIONS; MG2+ HOMEOSTASIS;
D O I
10.1038/aps.2011.60
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Searching for effective pharmacological agents for stroke treatment has largely been unsuccessful. Despite initial excitement, antagonists for glutamate receptors, the most studied receptor channels in ischemic stroke, have shown insufficient neuroprotective effects in clinical trials. Outside the traditional glutamate-mediated excitotoxicity, recent evidence suggests few non-glutamate mechanisms, which may also cause ionic imbalance and cell death in cerebral ischemia. Transient receptor potential melastatin 7 (TRPM7) is a Ca2+ permeable, non-selective cation channel that has recently gained attention as a potential cation influx pathway involved in ischemic events. Compelling new evidence from an in vivo study demonstrated that suppression of TRPM7 channels in adult rat brain in vivo using virally mediated gene silencing approach reduced delayed neuronal cell death and preserved neuronal functions in global cerebral ischemia. In this review, we will discuss the current understanding of the role of TRPM7 channels in physiology and pathophysiology as well as its therapeutic potential in stroke.
引用
收藏
页码:725 / 733
页数:9
相关论文
共 88 条
[1]   A key role for TRPM7 channels in anoxic neuronal death [J].
Aarts, M ;
Iihara, K ;
Wei, WL ;
Xiong, ZG ;
Arundine, M ;
Cerwinski, W ;
MacDonald, JF ;
Tymianski, M .
CELL, 2003, 115 (07) :863-877
[2]   TRPMs and neuronal cell death [J].
Aarts, MM ;
Tymianski, M .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2005, 451 (01) :243-249
[3]   TRPM7 and ischemic CNS injury [J].
Aarts, MM ;
Tymianski, M .
NEUROSCIENTIST, 2005, 11 (02) :116-123
[4]   Importance of melastatin-like transient receptor potential 7 and cations (magnesium, calcium) in human osteoblast-like cell proliferation [J].
Abed, E. ;
Moreau, R. .
CELL PROLIFERATION, 2007, 40 (06) :849-865
[5]   Role of 5-lipoxygenase in myocardial ischemia-reperfusion injury in mice [J].
Adamek, Anna ;
Jung, Susanne ;
Dienesch, Charlotte ;
Laser, Martin ;
Ertl, Georg ;
Bauersachs, Johann ;
Frantz, Stefan .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2007, 571 (01) :51-54
[6]  
[Anonymous], 2000, COCHRANE DB SYST REV
[7]  
[Anonymous], STROKE
[8]   Reasons why few patients with acute stroke receive tissue plasminogen activator [J].
Bambauer, Kara Z. ;
Johnston, S. Claiborne ;
Bambauer, Derek E. ;
Zivin, Justin A. .
ARCHIVES OF NEUROLOGY, 2006, 63 (05) :661-664
[9]   Beyond NMDA and AMPA glutamate receptors: emerging mechanisms for ionic imbalance and cell death in stroke [J].
Besancon, Elaine ;
Guo, Shuzhen ;
Lok, Josephine ;
Tymianski, Michael ;
Lo, Eng H. .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2008, 29 (05) :268-275
[10]   Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years [J].
Carandang, Raphael ;
Seshadri, Sudha ;
Beiser, Alexa ;
Kelly-Hayes, Margaret ;
Kase, Carlos S. ;
Kannel, William B. ;
Wolf, Philip A. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2006, 296 (24) :2939-2946