Haughey Norman J, Zhu Xiaomao, Bandaru Veera Venkata Ratnam
Department of Neurology, Division of Neuroimmunology and Neurological Infections, The Johns Hopkins University School of Medicine, Pathology 517, 600 North Wolfe Street, Baltimore, MD, 21287, USA,
J Neuroimmune Pharmacol. 2013 Dec;8(5):1136-46. doi: 10.1007/s11481-013-9506-0. Epub 2013 Nov 8.
The development and application of biomarkers to neurodegenerative diseases has become increasingly important in clinical practice and therapeutic trials. While substantial progress has been made at the basic science level in understanding the pathophysiology of HIV-Associated Neurocognitive Disorders (HAND), there are significant limitations in our current ability to predict the onset or trajectory of disease, and to accurately determine the effects of therapeutic interventions. Thus, the development of objective biomarkers is critical to further our understanding and treatment of HAND. In recent years, biomarker discovery efforts have largely been driven forward through the implementation of multiple "omics" approaches that include (but are not restricted to): Lipidomics, proteomics, metabolomics, genomics, transcriptomics, and advances in brain imaging approaches such as functional connectomics. In this paper we summarize our progress to date on lipidomic approaches to biomarker discovery, discuss how these data have influenced basic research on the neuropathology of HAND, and implications for the development of therapeutics that target metabolic pathways involved in lipid handling.
生物标志物在神经退行性疾病中的开发与应用在临床实践和治疗试验中变得越来越重要。虽然在理解与HIV相关的神经认知障碍(HAND)的病理生理学的基础科学层面已经取得了实质性进展,但我们目前预测疾病发作或病程以及准确确定治疗干预效果的能力存在重大局限性。因此,开发客观的生物标志物对于深化我们对HAND的理解和治疗至关重要。近年来,生物标志物的发现工作很大程度上是通过实施多种“组学”方法推动的,这些方法包括(但不限于):脂质组学、蛋白质组学、代谢组学、基因组学、转录组学,以及脑成像方法的进展,如功能连接组学。在本文中,我们总结了迄今为止在脂质组学方法用于生物标志物发现方面取得的进展,讨论了这些数据如何影响HAND神经病理学的基础研究,以及对针对脂质处理相关代谢途径的治疗方法开发的意义。