Roucou Xavier, Gains Malcolm, LeBlanc Andréa C
Bloomfield Center for Research in Aging, Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal, Québec, Canada.
Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada.
J Neurosci Res. 2004 Jan 15;75(2):153-161. doi: 10.1002/jnr.10864.
The normal function of prion protein (PrP) is usually disregarded at the expense of the more fascinating role of PrP in transmissible prion diseases. However, the normal PrP may play an important role in cellular function in the central nervous system, since PrP is highly expressed in neurons and motifs in the sequence of PrP are conserved in evolution. The finding that prion null mice do not have a significant overt phenotype suggests that the normal function of PrP is of minor importance. However, the absence of PrP in cells or in vivo contributes to an increased susceptibility to oxidative stress or apoptosis-inducing insults. An alternative explanation is that the PrP normal function is so important that it is redundant. Probing into the characteristics of PrP has revealed a number of features that could mediate important cellular functions. The neuroprotective actions so far identified with PrP are initiated through cell surface signaling, antioxidant activity, or anti-Bax function. Here, we review the characteristics of the PrP and the evidence that PrP protects against neurodegeneration and neuronal cell death.
朊病毒蛋白（PrP）的正常功能通常被忽视，人们更关注PrP在传染性朊病毒疾病中更引人入胜的作用。然而，正常的PrP可能在中枢神经系统的细胞功能中发挥重要作用，因为PrP在神经元中高度表达，且PrP序列中的基序在进化过程中是保守的。朊病毒基因敲除小鼠没有明显的显性表型这一发现表明，PrP的正常功能不太重要。然而，细胞或体内缺乏PrP会导致对氧化应激或诱导凋亡的损伤的易感性增加。另一种解释是，PrP的正常功能非常重要，以至于它是多余的。对PrP特征的探究揭示了许多可能介导重要细胞功能的特性。目前已确定的PrP的神经保护作用是通过细胞表面信号传导、抗氧化活性或抗Bax功能启动的。在这里，我们综述了PrP的特征以及PrP预防神经退行性变和神经元细胞死亡的证据。
