Lezoualc'h F, Behl C
Max Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.
Mol Psychiatry. 1998 Jan;3(1):15-20. doi: 10.1038/sj.mp.4000295.
It is now well established that a number of neurological disorders such as Parkinson's disease and Alzheimer's disease are characterized by the formation of reactive oxygen species (ROS). When produced in excess, ROS can induce oxidative damage to cellular macromolecules and ultimately cell death. Cells 'employ a number of defense systems against oxidative damage, including antioxidants and antioxidant enzymes. In an effort to develop a better understanding of the molecular mechanisms of the cellular response to a challenge by ROS as observed under certain neuropathological conditions, recent studies have focused on the regulation of gene expression by neurotoxins, including oxidative stressors. One transcription factor that can be activated by oxidative stress is the nuclear transcription factor-kappa B (NF-kappaB). Initially, this factor has been shown to play a major role in the activation of defensive genes during immune and inflammatory responses. But as evidence accumulates suggesting a close association of NF-kappaB activation also with the neuropathology occurring in neurodegenerative processes and neuronal cell death, the search is on to define potential roles for this transcription factor that are specific for neurons. The present article summarizes some of the recent studies that are trying to clarify NF-kappaB's role during neuronal degeneration.
现在已经充分证实，一些神经系统疾病，如帕金森病和阿尔茨海默病，其特征是活性氧（ROS）的形成。当ROS产生过多时，会诱导对细胞大分子的氧化损伤并最终导致细胞死亡。细胞“采用”多种防御系统来抵御氧化损伤，包括抗氧化剂和抗氧化酶。为了更好地理解在某些神经病理条件下观察到的细胞对ROS挑战的分子反应机制，最近的研究集中在神经毒素（包括氧化应激源）对基因表达的调控上。一种可被氧化应激激活的转录因子是核转录因子-κB（NF-κB）。最初，该因子已被证明在免疫和炎症反应期间防御基因的激活中起主要作用。但随着越来越多的证据表明NF-κB的激活也与神经退行性过程中发生的神经病理学和神经元细胞死亡密切相关，人们正在寻找该转录因子在神经元中的特定潜在作用。本文总结了一些近期试图阐明NF-κB在神经元变性过程中作用的研究。
