Tedeschi Andrea, Di Giovanni Simone
Laboratory for NeuroRegeneration and Repair, Department of Neurology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Otfried-Mueller Strasse 27, Tuebingen D-72076, Germany.
EMBO Rep. 2009 Jun;10(6):576-83. doi: 10.1038/embor.2009.89. Epub 2009 May 8.
The transcription factor p53 protects neurons from transformation and DNA damage through the induction of cell-cycle arrest, DNA repair and apoptosis in a range of in vitro and in vivo conditions. Indeed, p53 has a crucial role in eliciting neuronal cell death during development and in adult organisms after exposure to a range of stressors and/or DNA damage. Nevertheless, accumulating evidence challenges this one-sided view of the role of p53 in the nervous system. Here, we discuss how-unexpectedly-p53 can regulate the proliferation and differentiation of neural progenitor cells independently of its role in apoptosis, and p53 post-translational modifications might promote neuronal maturation, as well as axon outgrowth and regeneration, following neuronal injury. We hope to encourage a more comprehensive view of the non-apoptotic functions of p53 during neural development, and to warn against oversimplifications regarding its role in neurons. In addition, we discuss how further insight into the p53-dependent modulation of these mechanisms is necessary to elucidate the decision-making processes between neuronal cell death and differentiation during development, and between neuronal degeneration and axonal regeneration after injury.
转录因子p53在一系列体外和体内条件下，通过诱导细胞周期停滞、DNA修复和凋亡，保护神经元免于转化和DNA损伤。事实上，p53在发育过程中以及成年生物体暴露于一系列应激源和/或DNA损伤后引发神经元细胞死亡方面起着关键作用。然而，越来越多的证据对p53在神经系统中作用的这种片面观点提出了挑战。在这里，我们讨论了p53如何出乎意料地独立于其在凋亡中的作用来调节神经祖细胞的增殖和分化，以及p53的翻译后修饰可能如何促进神经元成熟以及神经元损伤后的轴突生长和再生。我们希望鼓励对p53在神经发育过程中的非凋亡功能有更全面的认识，并警告不要对其在神经元中的作用进行过度简化。此外，我们讨论了进一步深入了解p53对这些机制的依赖性调节对于阐明发育过程中神经元细胞死亡和分化之间以及损伤后神经元变性和轴突再生之间的决策过程是如何必要的。
