摘要
线粒体脱氢酶(ALDH2)是一种乙醛脱氢酶(ALDH)的同工酶,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,诸如4-羟基-2-壬烯醛和丙二醛等有毒醛的累积被认为是心肌和脑I/R损伤的一种重要机制。 在这些ALDH的同工酶中,ALDH2被认为在清除有毒醛上发挥着重大作用。因此,ALDH2可能是一个保护心脏和大脑I/R损伤的潜在的药物。的确,一些新确定的LADH2催化剂(如Alda1)显示了对心脏和大脑I/R损伤的有益作用。此外,ALDH在某些干细胞或祖细胞中展示了高水平活性,这些细胞被称为ALDH bright (ALDHbr)细胞,在治疗心肌缺血患者上具有潜在价值。本文的主要目的:1,总结ALDH2在心脏和大脑I/R损伤中起保护作用的近期发现;2,列举可用的有效力、选择性和临床潜力的ALDH2催化剂;3,为具有临床治疗价值的ALDHbr细胞提供合理性。
关键词: 4-羟基-2-壬烯醛(4-HNE),Alda-1,醛,缺血/再灌注损伤,线粒体脱氢酶(ALDH2),氧化应激
Current Drug Targets
Title:Mitochondrial Aldehyde Dehydrogenase, A Potential Drug Target for Protection of Heart and Brain from Ischemia/Reperfusion Injury
Volume: 15 Issue: 10
Author(s): Xiu-Ju Luo, Bin Liu, Qi-Lin Ma and Jun Peng
Affiliation:
关键词: 4-羟基-2-壬烯醛(4-HNE),Alda-1,醛,缺血/再灌注损伤,线粒体脱氢酶(ALDH2),氧化应激
摘要: 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 (ALDHbr) 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 ALDHbr cells in clinical therapeutic value.
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Cite this article as:
Luo Xiu-Ju, Liu Bin, Ma Qi-Lin and Peng Jun, Mitochondrial Aldehyde Dehydrogenase, A Potential Drug Target for Protection of Heart and Brain from Ischemia/Reperfusion Injury, Current Drug Targets 2014; 15 (10) . https://dx.doi.org/10.2174/1389450115666140828142401
DOI https://dx.doi.org/10.2174/1389450115666140828142401 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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