Picklo Matthew J, Montine Thomas J, Amarnath Venkataraman, Neely M Diana
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Science, Grand Forks 58203, USA.
Toxicol Appl Pharmacol. 2002 Nov 1;184(3):187-97. doi: 10.1006/taap.2002.9506.
A large amount of data has implicated reactive carbonyls as neurotoxic mediators of oxidative damage in the progression of Alzheimer's disease (AD) and other neurodegenerative diseases. The oxidation of polyunsaturated fatty acids, reducing sugars, and amino acids leads to the formation of carbonyls and carbonyl adduction products such as 4-hydroxy-2-nonenal (HNE), advanced glycation end products (AGEs), and protein-bound carbonyls. Levels of these products are elevated in AD. In this review, we examine the role that carbonyls may play in the development of this disease. We focus upon the chemistry of these molecules and the evidence for their involvement in AD. The biological effects of these carbonyl species in model systems and their relationship to AD are discussed. Lastly, we examine the potential mechanisms that the brain utilizes to detoxify carbonyl species and possible therapeutic interventions based on carbonyl detoxification.
大量数据表明，活性羰基化合物是阿尔茨海默病（AD）和其他神经退行性疾病进展过程中氧化损伤的神经毒性介质。多不饱和脂肪酸、还原糖和氨基酸的氧化会导致羰基化合物和羰基加成产物的形成，如4-羟基-2-壬烯醛（HNE）、晚期糖基化终产物（AGEs）和蛋白质结合羰基。这些产物的水平在AD中升高。在本综述中，我们研究了羰基化合物在该疾病发展过程中可能发挥的作用。我们重点关注这些分子的化学性质以及它们与AD相关的证据。讨论了这些羰基物质在模型系统中的生物学效应及其与AD的关系。最后，我们研究了大脑用于解毒羰基物质的潜在机制以及基于羰基解毒的可能治疗干预措施。
