Abstract
Ischemic stroke causes a heavy health burden worldwide, with over 10 million new cases every year. Despite the high prevalence and mortality rate of ischemic stroke, the underlying molecular mechanisms for the common etiological factors of ischemic stroke and ischemic stroke itself remain unclear, which results in insufficient preventive strategies and ineffective treatments for this devastating disease. In this review, we demonstrate that transient receptor potential cation channel, subfamily M, member 2 (TRPM2), a non-selective ion channel activated by oxidative stress, is actively involved in all the important steps in the etiology and pathology of ischemic stroke. TRPM2 could be a promising target in screening more effective prophylactic strategies and therapeutic medications for ischemic stroke.
Highlights
Stroke is a common cause of death and mortality only secondary to myocardial infarction, and is the third-most-common cause of disability [1]
TRPM2 is ubiquitously expressed in almost all tissues and cell types [48], and TRPM2mediated Ca2+ signaling is involved in various important cellular functions, including cytokine/hormone secretion [31,49], cytoskeletal rearrangement [32], cell migration [50], regulation of reactive oxygen species (ROS) production [51], autophagy [52], inflammasome activation [49], and cell death [53]
Aging-related chronic inflammation is critical in the development of many cardiovascular diseases [74], and previously we found that the expression of TRPM2 was significantly increased in atrial fibroblasts isolated from patients with Atrial fibrillation (AF) compared with that from nonAF patients [78]
Summary
Stroke is a common cause of death and mortality only secondary to myocardial infarction, and is the third-most-common cause of disability [1]. Recent TRPM2 structures reveal that in zebrafish (Danio rerio) TRPM2 (drTRPM2), besides the NUDT9-H domain, there is another ADPR binding site at the N terminal MHR1/2 domain [40]. The local temperature in the affected tissue during inflammation usually increases [46], and oxidative-stress-mediated Ca2+ signaling is critical for the elicitation of inflammatory responses in immune cells [47]. TRPM2 is ubiquitously expressed in almost all tissues and cell types [48], and TRPM2mediated Ca2+ signaling is involved in various important cellular functions, including cytokine/hormone secretion [31,49], cytoskeletal rearrangement [32], cell migration [50], regulation of reactive oxygen species (ROS) production [51], autophagy [52], inflammasome activation [49], and cell death [53]. Almost all the above diseases are the upstream etiological factors for ischemic stroke [68], highlighting the critical and comprehensive role of TRPM2 in the development and progression of this devastating disease
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