p53 is a key modulator of cellular stress responses.It is activated in the ischemic areas of brain,and contributes to neuronal apoptosis.In various stroke models,p53 deficiency or applications of p53 inhibitors can si...p53 is a key modulator of cellular stress responses.It is activated in the ischemic areas of brain,and contributes to neuronal apoptosis.In various stroke models,p53 deficiency or applications of p53 inhibitors can significantly attenuate brain damage.p53-mediated neuronal apoptosis occurs through various molecular mechanisms.The transcriptional pathway is an important mechanism through which p53 induces neuronal apoptosis by up-regulating the expression of its target gene p21WAF,Peg3/Pw1 or p53-up-regulated modulator of apoptosis （PUMA） .In addition,p53 disrupts NF-κB binding to p300 and blocks NF-κB-mediated survival signaling.On the other hand,the transcription-independent pathway mechanism is also of great importance.In this pathway,p53 is translocated to mitochondrial and mediates the release of cytochrome c.In both pathways,p53 seems to play a key role in post-ischemic brain damage and has become a therapeutic target against stroke pathology.展开更多
基金supported by the National Natural Science Foundation of China(No.30973510)the Personnel Affairs Bureau of Jiangsu Province,China(No.BU134601)
文摘p53 is a key modulator of cellular stress responses.It is activated in the ischemic areas of brain,and contributes to neuronal apoptosis.In various stroke models,p53 deficiency or applications of p53 inhibitors can significantly attenuate brain damage.p53-mediated neuronal apoptosis occurs through various molecular mechanisms.The transcriptional pathway is an important mechanism through which p53 induces neuronal apoptosis by up-regulating the expression of its target gene p21WAF,Peg3/Pw1 or p53-up-regulated modulator of apoptosis （PUMA） .In addition,p53 disrupts NF-κB binding to p300 and blocks NF-κB-mediated survival signaling.On the other hand,the transcription-independent pathway mechanism is also of great importance.In this pathway,p53 is translocated to mitochondrial and mediates the release of cytochrome c.In both pathways,p53 seems to play a key role in post-ischemic brain damage and has become a therapeutic target against stroke pathology.
