Luo Xiu-Ju, Liu Bin, Ma Qi-Lin, Peng Jun
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University. No.110 Xiang-Ya Road, Changsha, 410078, China.
Curr Drug Targets. 2014;15(10):948-55.
Mitochondrial aldehyde dehydrogenase (ALDH2) is an isoenzyme of aldehyde dehydrogenases (ALDH), a group of enzymes that are responsible for clearance of aldehydes in the body. In animal myocardial or cerebral ischemia/ reperfusion (I/R) models, accumulation of toxic aldehydes, such as 4-hydroxy-2-nonenal and malondialdehyde, is thought to be an important mechanism for myocardial and cerebral I/R injury. Among the isoenzymes of ALDH, ALDH2 is believed to play a major role in clearance of toxic aldehydes. Thus, ALDH2 might be a potential drug target for protection of the heart or brain from I/R injury. Indeed, some of the newly identified ALDH2 activators (such as Alda-1) have demonstrated beneficial effects on heart and brain I/R injury. In addition, ALDH activity is present at high levels in some stem or progenitor cells, known as ALDH bright (ALDH(br)) cells, which possess potential value in treating patients with myocardial ischemia. The main purpose of this review is 1) to summarize recent findings regarding the role of ALDH2 in protection of heart or brain from I/R injury, 2) to list the available ALDH2 activators with their potency, selectivity and clinical potentials, and 3) to provide a rationale for ALDH(br) cells in clinical therapeutic value.
线粒体醛脱氢酶（ALDH2）是醛脱氢酶（ALDH）的一种同工酶，ALDH是一组负责清除体内醛类的酶。在动物心肌或脑缺血/再灌注（I/R）模型中，有毒醛类如4-羟基壬烯醛和丙二醛的积累被认为是心肌和脑I/R损伤的重要机制。在ALDH的同工酶中，ALDH2被认为在清除有毒醛类中起主要作用。因此，ALDH2可能是保护心脏或大脑免受I/R损伤的潜在药物靶点。事实上，一些新发现的ALDH2激活剂（如Alda-1）已显示出对心脏和脑I/R损伤的有益作用。此外，在一些干细胞或祖细胞中，即所谓的ALDH高表达（ALDH(br)）细胞中，ALDH活性水平很高，这些细胞在治疗心肌缺血患者方面具有潜在价值。本综述的主要目的是：1）总结关于ALDH2在保护心脏或大脑免受I/R损伤中作用的最新研究结果；2）列出可用的ALDH2激活剂及其效力、选择性和临床潜力；3）为ALDH(br)细胞的临床治疗价值提供理论依据。
