Developmental Biology Laboratory, Maisonneuve-Rosemont Hospital, 5415 Boulevard l'Assomption, Montréal, Canada.
Antioxid Redox Signal. 2011 Sep 15;15(6):1729-37. doi: 10.1089/ars.2010.3610. Epub 2011 Mar 31.
Recent advances in delineating the biological functions of p53 had shed the light on its key role in the multifacets of cellular homeostasis. After its activation, via DNA damage, oxidative stress, or aberrant expression of oncogenes, p53 transduces its classical effect through several mechanisms comprising activation of the DNA repair machinery, cell cycle arrest, and initiation of apoptosis or senescence. In the mammalian brain, p53 plays critical functions in normal development, tumor suppression, neurodegenerative diseases, and aging. Herein, we focus on the constitutive pro-oxidant activity of p53 in neurons and discuss the potential implication of this finding in the context of neurodegenerative diseases and normal brain aging.
近年来,p53 生物学功能的研究进展揭示了其在细胞稳态多方面的关键作用。p53 通过 DNA 损伤、氧化应激或癌基因异常表达被激活后,通过包括激活 DNA 修复机制、细胞周期停滞以及启动细胞凋亡或衰老等几种机制来传递其经典效应。在哺乳动物大脑中,p53 在正常发育、肿瘤抑制、神经退行性疾病和衰老中发挥着关键作用。本文我们重点关注 p53 在神经元中的组成性促氧化剂活性,并讨论这一发现对神经退行性疾病和正常大脑衰老的潜在意义。