Dose Janina, Huebbe Patricia, Nebel Almut, Rimbach Gerald
Institute of Human Nutrition and Food Science, Kiel University, Hermann-Rodewald-Str. 6, D-24118, Kiel, Germany.
Institute of Clinical Molecular Biology, Kiel University, Schittenhelmstr. 12, D-24105, Kiel, Germany.
Lipids Health Dis. 2016 Jul 25;15:121. doi: 10.1186/s12944-016-0288-2.
The APOE gene is one of currently only two genes that have consistently been associated with longevity. Apolipoprotein E (APOE) is a plasma protein which plays an important role in lipid and lipoprotein metabolism. In humans, there are three major APOE isoforms, designated APOE2, APOE3, and APOE4. Of these three isoforms, APOE3 is most common while APOE4 was shown to be associated with age-related diseases, including cardiovascular and Alzheimer's disease, and therefore an increased mortality risk with advanced age. Evidence accumulates, showing that oxidative stress and, correspondingly, mitochondrial function is affected in an APOE isoform-dependent manner. Accordingly, several stress response pathways implicated in the aging process, including the endoplasmic reticulum stress response and immune function, appear to be influenced by the APOE genotype. The investigation and development of treatment strategies targeting APOE4 have not resolved any therapeutic yet that could be entirely recommended. This mini-review provides an overview on the state of research concerning the impact of the APOE genotype on stress response-related processes, emphasizing the strong interconnection between mitochondrial function, endoplasmic reticulum stress and the immune response. Furthermore, this review addresses potential treatment strategies and associated pitfalls as well as lifestyle interventions that could benefit people with an at risk APOE4 genotype.
载脂蛋白E（APOE）基因是目前仅有的两个一直与长寿相关的基因之一。载脂蛋白E（APOE）是一种血浆蛋白，在脂质和脂蛋白代谢中起重要作用。在人类中，有三种主要的APOE异构体，分别命名为APOE2、APOE3和APOE4。在这三种异构体中，APOE3最为常见，而APOE4与包括心血管疾病和阿尔茨海默病在内的与年龄相关的疾病有关，因此随着年龄增长死亡风险增加。越来越多的证据表明，氧化应激以及相应的线粒体功能以APOE异构体依赖的方式受到影响。因此，衰老过程中涉及的几种应激反应途径，包括内质网应激反应和免疫功能，似乎都受到APOE基因型的影响。针对APOE4的治疗策略的研究和开发尚未找到任何完全值得推荐的治疗方法。这篇小型综述概述了关于APOE基因型对应激反应相关过程影响的研究现状，强调了线粒体功能、内质网应激和免疫反应之间的紧密联系。此外，本综述还讨论了潜在的治疗策略、相关的陷阱以及可能使有APOE4基因型风险的人受益的生活方式干预措施。
