p53-mediated neuronal cell death in ischemic brain injury.
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 p21(WAF), Peg3/Pw1 or p53-up-regulated modulator of apoptosis (PUMA). In addition, p53 disrupts NF-kappaB binding to p300 and blocks NF-kappaB-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.
Hong
Li-Zhi
LZ
Department of Pharmacology, Laboratory of Aging and Nervous Diseases, Soochow University School of Medicine, Suzhou 215123, China.
Zhao
Xiao-Yuan
XY
Zhang
Hui-Ling
HL
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D016923:Cell Death / Q000502:physiology; D006801:Humans; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53