Trushina Eugenia, Mielke Michelle M
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA; Department of Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.
Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic, Rochester, MN 55905, USA.
Biochim Biophys Acta. 2014 Aug;1842(8):1232-9. doi: 10.1016/j.bbadis.2013.06.014. Epub 2013 Jun 29.
The pathophysiological changes associated with Alzheimer's Disease (AD) begin decades before the emergence of clinical symptoms. Understanding the early mechanisms associated with AD pathology is, therefore, especially important for identifying disease-modifying therapeutic targets. While the majority of AD clinical trials to date have focused on anti-amyloid-beta (Aβ) treatments, other therapeutic approaches may be necessary. The ability to monitor changes in cellular networks that include both Aβ and non-Aβ pathways is essential to advance our understanding of the etiopathogenesis of AD and subsequent development of cognitive symptoms and dementia. Metabolomics is a powerful tool that detects perturbations in the metabolome, a pool of metabolites that reflects changes downstream of genomic, transcriptomic and proteomic fluctuations, and represents an accurate biochemical profile of the organism in health and disease. The application of metabolomics could help to identify biomarkers for early AD diagnosis, to discover novel therapeutic targets, and to monitor therapeutic response and disease progression. Moreover, given the considerable parallel between mouse and human metabolism, the use of metabolomics provides ready translation of animal research into human studies for accelerated drug design. In this review, we will summarize current progress in the application of metabolomics in both animal models and in humans to further understanding of the mechanisms involved in AD pathogenesis.
与阿尔茨海默病（AD）相关的病理生理变化在临床症状出现前数十年就已开始。因此，了解与AD病理相关的早期机制对于确定疾病修饰治疗靶点尤为重要。虽然迄今为止大多数AD临床试验都集中在抗淀粉样β蛋白（Aβ）治疗上，但可能需要其他治疗方法。监测包括Aβ和非Aβ途径在内的细胞网络变化的能力对于推进我们对AD病因发病机制以及随后认知症状和痴呆症发展的理解至关重要。代谢组学是一种强大的工具，可检测代谢组中的扰动，代谢组是一组代谢物，反映了基因组、转录组和蛋白质组波动下游的变化，并代表了生物体在健康和疾病状态下的准确生化特征。代谢组学的应用有助于识别早期AD诊断的生物标志物，发现新的治疗靶点，并监测治疗反应和疾病进展。此外，鉴于小鼠和人类代谢之间存在相当大的相似性，代谢组学的使用为将动物研究快速转化为人体研究以加速药物设计提供了便利。在这篇综述中，我们将总结代谢组学在动物模型和人类中的应用现状，以进一步了解AD发病机制中涉及的机制。
