Morrison R S, Kinoshita Y
Department of Neurological Surgery, University of Washington School of Medicine, Box 356470, Seattle, Washington 98195-6470, USA.
Cell Death Differ. 2000 Oct;7(10):868-79. doi: 10.1038/sj.cdd.4400741.
The p53 tumor suppressor gene is a sequence-specific transcription factor that activates the expression of genes engaged in promoting growth arrest or cell death in response to genotoxic stress. A possible role for p53-related modulation of neuronal viability has been suggested by the finding that p53 expression is elevated in damaged neurons in acute models of injury such as ischemia and epilepsy and in brain tissue samples derived from patients with chronic neurodegenerative diseases. Moreover, the absence of p53 has been shown to protect neurons from a wide variety of acute toxic insults. Signal transduction pathways associated with p53-induced cell death are being unraveled and suggest that intervention may prove fruitful in maintaining neuronal viability and restoring function following cytopathic insults.
p53肿瘤抑制基因是一种序列特异性转录因子,可激活那些在基因毒性应激反应中参与促进生长停滞或细胞死亡的基因的表达。p53相关的神经元生存能力调节的可能作用已通过以下发现得到提示:在诸如局部缺血和癫痫等急性损伤模型的受损神经元以及来自慢性神经退行性疾病患者的脑组织样本中,p53表达升高。此外,已表明缺乏p53可保护神经元免受多种急性毒性损伤。与p53诱导的细胞死亡相关的信号转导途径正在被阐明,这表明干预措施可能在维持神经元生存能力以及在细胞病变性损伤后恢复功能方面取得成效。