The unfolded protein response, inflammation, oscillators, and disease: a systems biology approach

IF 0.7
R. Rangel‐Aldao
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引用次数: 3

Abstract

Abstract Non-communicable diseases (NCDs) such as cardiovascular disease, cancers, diabetes and obesity are responsible for about two thirds of mortality worldwide, and all of these ailments share a common low-intensity systemic chronic inflammation, endoplasmic reticulum stress (ER stress), and the ensuing Unfolded Protein Response (UPR). These adaptive mechanisms are also responsible for significant metabolic changes that feedback with the central clock of the suprachiasmatic nucleus (SCN) of the hypothalamus, as well as with oscillators of peripheral tissues. In this review we attempt to use a systems biology approach to explore such interactions as a whole; to answer two fundamental questions: (1) how dependent are these adaptive responses and subsequent events leading to NCD with their state of synchrony with the SCN and peripheral oscillators? And, (2) How could modifiers of the activity of SCN for instance, food intake, exercise, and drugs, be potentially used to modulate systemic inflammation and ER stress to ameliorate or even prevent NCDs?
未折叠蛋白反应、炎症、振荡因子和疾病:系统生物学方法
非传染性疾病(ncd),如心血管疾病、癌症、糖尿病和肥胖,是全球约三分之二的死亡率的原因,所有这些疾病都有一个共同的低强度系统性慢性炎症、内质网应激(ER应激)和随后的未折叠蛋白反应(UPR)。这些适应性机制也负责与下丘脑视交叉上核(SCN)的中央时钟以及外周组织振荡器反馈的显著代谢变化。在这篇综述中,我们试图使用系统生物学的方法来探索这种相互作用作为一个整体;回答两个基本问题:(1)这些自适应反应和导致非传染性疾病的后续事件与它们与SCN和外围振荡器的同步状态有多大的依赖性?(2) SCN活性的调节剂(如食物摄入、运动和药物)如何可能被用于调节全身性炎症和内质网应激,以改善甚至预防非传染性疾病?
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