Department of Pharmacology, Laboratory of Aging and Nervous Diseases, Soochow University School of Medicine, Suzhou 215123, China.
Neurosci Bull. 2010 Jun;26(3):232-40. doi: 10.1007/s12264-010-1111-0.
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.
p53 是细胞应激反应的关键调节剂。它在脑缺血区域被激活，并促进神经元凋亡。在各种中风模型中，p53 缺失或应用 p53 抑制剂可以显著减轻脑损伤。p53 介导的神经元凋亡通过多种分子机制发生。转录途径是 p53 通过上调其靶基因 p21(WAF)、Peg3/Pw1 或 p53 上调凋亡调节剂 (PUMA) 的表达诱导神经元凋亡的重要机制。此外，p53 破坏 NF-κB 与 p300 的结合并阻断 NF-κB 介导的存活信号。另一方面，转录非依赖性途径机制也非常重要。在该途径中，p53 易位到线粒体并介导细胞色素 c 的释放。在这两条途径中，p53 似乎在缺血后脑损伤中发挥关键作用，并已成为对抗中风病理的治疗靶点。
