Department of Chemistry, Center of Membrane Sciences, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA.
Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy.
Free Radic Biol Med. 2013 Sep;62:157-169. doi: 10.1016/j.freeradbiomed.2012.09.027. Epub 2012 Oct 5.
Lipid peroxidation involves a cascade of reactions in which production of free radicals occurs selectively in the lipid components of cellular membranes. Polyunsaturated fatty acids easily undergo lipid peroxidation chain reactions, which, in turn, lead to the formation of highly reactive electrophilic aldehydes. Among these, the most abundant aldehydes are 4-hydroxy-2-nonenal (HNE) and malondialdehyde, while acrolein is the most reactive. Proteins are susceptible to posttranslational modifications caused by aldehydes binding covalently to specific amino acid residues, in a process called Michael adduction, and these types of protein adducts, if not efficiently removed, may be, and generally are, dangerous for cellular homeostasis. In the present review, we focused the discussion on the selective proteins that are identified, by redox proteomics, as selective targets of HNE modification during the progression and pathogenesis of Alzheimer disease (AD). By comparing results obtained at different stages of the AD, it may be possible to identify key biochemical pathways involved and ideally identify therapeutic targets to prevent, delay, or treat AD.
脂质过氧化反应涉及一系列反应，其中自由基的产生在细胞膜的脂质成分中选择性地发生。多不饱和脂肪酸容易发生脂质过氧化链式反应，这反过来又导致高反应性亲电醛的形成。在这些醛中，最丰富的醛是 4-羟基-2-壬烯醛 (HNE) 和丙二醛，而丙烯醛是最具反应性的。醛通过与特定氨基酸残基共价结合导致蛋白质易发生翻译后修饰，这一过程称为 Michael 加成，这些类型的蛋白质加合物，如果不能有效地去除，可能而且通常对细胞内稳态是危险的。在本综述中，我们通过氧化还原蛋白质组学重点讨论了在阿尔茨海默病（AD）的进展和发病机制中被鉴定为 HNE 修饰的选择性蛋白质。通过比较 AD 不同阶段的结果，可能可以确定涉及的关键生化途径，并理想地确定预防、延迟或治疗 AD 的治疗靶点。
