Guan Zhi-zhong
Department of Molecular Biology and Pathology, Guiyang Medical University, Guiyang 550004, China.
Acta Pharmacol Sin. 2008 Jul;29(7):773-80. doi: 10.1111/j.1745-7254.2008.00819.x.
Alzheimer's disease (AD) is the most common neurodegenerative disorder, and its pathogenesis is likely to be associated with multiple etiologies and mechanisms in which oxidative stress and deficits of neurotransmitter receptors may play important roles. It has been indicated that a high level of free radicals can influence the expressions of nicotinic receptors (nAChRs), muscarinic receptors (mAChRs), and N-methyl-D-aspartate (NMDA) receptors, exhibiting disturbances of cellular membrane by lipid peroxidation, damages of the protein receptors by protein oxidation, and possible modified gene expressions of these receptors by DNA oxidation. nAChRs have shown an antioxidative effect by a direct or an indirect pathway; mAChR stimulation may generate reactive oxygen species, which might be a physiological compensative reaction, or improve oxidative stress; and high stimulation to NMDA receptors can increase the sensitivity of oxidative stress of neurons. This review may provide complemental information for understanding the correlation between oxidative stress and changed cholinergic and glutaminergic receptors in AD processing, and for revealing the underlying molecular mechanisms of these factors in the multiple etiologies and pathophysiology of the disorder.
阿尔茨海默病（AD）是最常见的神经退行性疾病，其发病机制可能与多种病因和机制相关，其中氧化应激和神经递质受体缺陷可能起重要作用。已有研究表明，高水平的自由基可影响烟碱型受体（nAChRs）、毒蕈碱型受体（mAChRs）和N-甲基-D-天冬氨酸（NMDA）受体的表达，通过脂质过氧化表现出细胞膜的紊乱，通过蛋白质氧化造成蛋白质受体的损伤，并可能通过DNA氧化改变这些受体的基因表达。nAChRs已通过直接或间接途径显示出抗氧化作用；mAChR刺激可能产生活性氧，这可能是一种生理补偿反应，或改善氧化应激；对NMDA受体的高刺激可增加神经元氧化应激的敏感性。本综述可为理解氧化应激与AD病程中胆碱能和谷氨酸能受体变化之间的相关性提供补充信息，并为揭示这些因素在该疾病多种病因和病理生理学中的潜在分子机制提供帮助。
