PDF(Pubmed)
Abstract：
Aldehyde dehydrogenase 2 (ALDH2) is an enzyme found in the mitochondrial matrix that plays a central role in alcohol and aldehyde metabolism. A common ALDH2 polymorphism in East Asians descent (called ALDH2*2 or E504K missense variant, SNP ID: rs671), present in approximately 8% of the world\'s population, has been associated with a variety of diseases. Recent meta-analyses support the relationship between this ALDH2 polymorphism and Alzheimer\'s disease (AD). And AD-like pathology observed in ALDH2-/- null mice and ALDH2*2 overexpressing transgenic mice indicate that ALDH2 deficiency plays an important role in the pathogenesis of AD. Recently, the worldwide increase in alcohol consumption has drawn attention to the relationship between heavy alcohol consumption and AD. Of potential clinical significance, chronic administration of alcohol in ALDH2*2/*2 knock-in mice exacerbates the pathogenesis of AD-like symptoms. Therefore, ALDH2 polymorphism and alcohol consumption likely play an important role in the onset and progression of AD. Here, we review the data on the relationship between ALDH2 polymorphism, alcohol, and AD, and summarize what is currently known about the role of the common ALDH2 inactivating mutation, ALDH2*2, and alcohol in the onset and progression of AD.
摘要：
醛脱氢酶2(ALDH2)是在线粒体基质中发现的酶,其在醇和醛代谢中起重要作用。东亚人后裔中常见的ALDH2多态性（称为ALDH2*2或E504K错义变体，SNPID：rs671），目前约占世界人口的8%，与多种疾病有关。最近的荟萃分析支持这种ALDH2多态性与阿尔茨海默病（AD）之间的关系。在ALDH2-/-null小鼠和ALDH2*2过表达的转基因小鼠中观察到的AD样病理表明ALDH2缺乏在AD的发病机理中起重要作用。最近,世界范围内酒精消费的增加引起了人们对大量饮酒与AD之间关系的关注。潜在的临床意义，ALDH2*2/*2敲入小鼠长期饮酒会加剧AD样症状的发病机制.因此,ALDH2多态性和饮酒可能在AD的发病和进展中起重要作用。这里,我们回顾了有关ALDH2多态性之间关系的数据，酒精,AD,并总结目前已知的常见ALDH2失活突变的作用，ALDH2*2和酒精在AD发病和进展中的作用。
