High-mobility group protein box-1 and its relevance to cerebral ischemia.
High-mobility group box-1 (HMGB1) was originally identified as a ubiquitously expressed, abundant, nonhistone DNA-binding protein. It has well-established functions in the maintenance of nuclear homeostasis. The HMGB1 can either be passively released into the extracellular milieu in response to necrotic signals or actively secreted in response to inflammatory signals. Extracellular HMGB1 interacts with receptors, including those for advanced glycation endproducts (RAGEs) as well as Toll-like receptor 2 (TLR2) and TLR4. The HMGB1 functions in a synergistic manner with other proinflammatory mediators and acts as a potent proinflammatory cytokine-like factor that contributes to the pathogenesis of diverse inflammatory and infectious disorders. Numerous reports point to HMGB1 as a novel player in the ischemic brain. This review provides an appraisal of the emerging roles of HMGB1 in cerebral ischemia injury, highlighting the relevance of HMGB1-blocking agents as potent therapeutic tools for neuroprotection.
Yang
Qing-wu
QW
Department of Neurology, Daping Hospital, The Third Military Medical University, Yuzhong District, Chongqing, China. Yangqwmlys@hotmail.com
Wang
Jing-Zhou
JZ
Li
Jing-Cheng
JC
Zhou
Yu
Y
Zhong
Qi
Q
Lu
Feng-Lin
FL
Xiang
Jing
J
D000818:Animals; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D024243:HMGB1 Protein / Q000737:chemistry / Q000378:metabolism*; D006801:Humans
D024243:HMGB1 Protein