Rashid Mohammad Abdur, Haque Mahmuda, Akbar Mohammed
Laboratory of Molecular Signaling, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, 20852, USA.
Department of Pharmacy, Southeast University, Dhaka, 1213, Bangladesh.
Adv Neurobiol. 2016;12:355-65. doi: 10.1007/978-3-319-28383-8_19.
Oxidative stress in the brain is the major cause of neurodegenerative disorders, including Alzheimer's, Parkinson's, Huntington's, and Creutzfeldt-Jakob diseases or amyotrophic lateral sclerosis. Under conditions of oxidative stress, the production of highly reactive oxygen species (ROS) overwhelms antioxidant defenses, resulting in the modification of macromolecules and their deposition in neuronal cell tissues. ROS plays an important role in neuronal cell death that they generate reactive aldehydes from membrane lipid peroxidation. Several neuronal diseases are associated with increased accumulation of abnormal protein adducts of reactive aldehydes, which mediate oxidative stress-linked pathological events, including cell growth inhibition and apoptosis induction. Combining findings on neurodegeneration and oxidative stress in Drosophila with studies on the metabolic characteristics of the human enzyme CBR1, it is clear now that CBR1 has a potential physiological role of neuroprotection in humans. Several studies suggest that CBR1 represents a significant pathway for the detoxification of reactive aldehydes derived from lipid peroxidation and that CBR1 in humans is essential for neuronal cell survival and to confer protection against oxidative stress-induced brain degeneration. Recently, it was discovered that HIF1alpha, AP-1, and Nrf2 could all regulate CBR1 at the transcriptional level. Nrf2 is known to regulate the transcription of antioxidant enzymes, and CBR1 functions as an antioxidant enzyme, suggesting that transcriptional regulation of CBR1 is a major contributor to the control of oxidative stress in neurodegeneration.
大脑中的氧化应激是神经退行性疾病的主要原因，包括阿尔茨海默病、帕金森病、亨廷顿病、克雅氏病或肌萎缩侧索硬化症。在氧化应激条件下，高活性氧（ROS）的产生超过了抗氧化防御能力，导致大分子发生修饰并沉积在神经元细胞组织中。ROS在神经元细胞死亡中起重要作用，它们通过膜脂质过氧化产生反应性醛类。几种神经疾病与反应性醛类的异常蛋白质加合物积累增加有关，这些加合物介导氧化应激相关的病理事件，包括细胞生长抑制和凋亡诱导。结合果蝇神经退行性变和氧化应激的研究结果以及对人类酶CBR1代谢特征的研究，现在很清楚CBR1在人类中具有潜在的神经保护生理作用。几项研究表明，CBR1是脂质过氧化衍生的反应性醛类解毒的重要途径，并且人类中的CBR1对于神经元细胞存活以及赋予针对氧化应激诱导的脑退化的保护至关重要。最近，人们发现HIF1α、AP - 1和Nrf2都可以在转录水平上调节CBR1。已知Nrf2调节抗氧化酶的转录，而CBR1作为一种抗氧化酶发挥作用，这表明CBR1的转录调节是神经退行性变中氧化应激控制的主要因素。
