Wilkins Jordan Maximillian, Trushina Eugenia
Mitochondrial Neurobiology and Therapeutics Laboratory, Department of Neurology, Mayo Clinic, Rochester, MN, United States.
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United States.
Front Neurol. 2018 Jan 12;8:719. doi: 10.3389/fneur.2017.00719. eCollection 2017.
Progress toward the development of efficacious therapies for Alzheimer's disease (AD) is halted by a lack of understanding early underlying pathological mechanisms. Systems biology encompasses several techniques including genomics, epigenomics, transcriptomics, proteomics, and metabolomics. Metabolomics is the newest omics platform that offers great potential for the diagnosis and prognosis of neurodegenerative diseases as an individual's metabolome reflects alterations in genetic, transcript, and protein profiles and influences from the environment. Advancements in the field of metabolomics have demonstrated the complexity of dynamic changes associated with AD progression underscoring challenges with the development of efficacious therapeutic interventions. Defining systems-level alterations in AD could provide insights into disease mechanisms, reveal sex-specific changes, advance the development of biomarker panels, and aid in monitoring therapeutic efficacy, which should advance individualized medicine. Since metabolic pathways are largely conserved between species, metabolomics could improve the translation of preclinical research conducted in animal models of AD into humans. A summary of recent developments in the application of metabolomics to advance the AD field is provided below.
由于对早期潜在病理机制缺乏了解,阿尔茨海默病(AD)有效治疗方法的研发进展受阻。系统生物学涵盖多种技术,包括基因组学、表观基因组学、转录组学、蛋白质组学和代谢组学。代谢组学是最新的组学平台,作为个体的代谢组反映了基因、转录本和蛋白质谱的变化以及环境影响,因此在神经退行性疾病的诊断和预后方面具有巨大潜力。代谢组学领域的进展表明,与AD进展相关的动态变化十分复杂,这凸显了开发有效治疗干预措施面临的挑战。确定AD中的系统水平改变可以深入了解疾病机制,揭示性别特异性变化,推动生物标志物组合的开发,并有助于监测治疗效果,这将推动个性化医疗的发展。由于代谢途径在物种间大多是保守的,代谢组学可以改善在AD动物模型中进行的临床前研究向人类的转化。以下是代谢组学应用于推动AD领域发展的近期进展总结。