Department of Neurology, Henry Ford Hospital, Detroit, MI, 48202, USA.
Department of Neurology, Henry Ford Hospital, Education & Research Building, Room 4023, 2799 W Grand Blvd, Detroit, MI, 48202, USA.
Cell Mol Life Sci. 2021 Apr;78(7):3181-3203. doi: 10.1007/s00018-020-03733-2. Epub 2021 Jan 15.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the nervous system that primarily affects young adults. Although the exact etiology of the disease remains obscure, it is clear that alterations in the metabolome contribute to this process. As such, defining a reliable and disease-specific metabolome has tremendous potential as a diagnostic and therapeutic strategy for MS. Here, we provide an overview of studies aimed at identifying the role of metabolomics in MS. These offer new insights into disease pathophysiology and the contributions of metabolic pathways to this process, identify unique markers indicative of treatment responses, and demonstrate the therapeutic effects of drug-like metabolites in cellular and animal models of MS. By and large, the commonly perturbed pathways in MS and its preclinical model include lipid metabolism involving alpha-linoleic acid pathway, nucleotide metabolism, amino acid metabolism, tricarboxylic acid cycle, D-ornithine and D-arginine pathways with collective role in signaling and energy supply. The metabolomics studies suggest that metabolic profiling of MS patient samples may uncover biomarkers that will advance our understanding of disease pathogenesis and progression, reduce delays and mistakes in diagnosis, monitor the course of disease, and detect better drug targets, all of which will improve early therapeutic interventions and improve evaluation of response to these treatments.
多发性硬化症(MS)是一种影响神经系统的炎症性脱髓鞘疾病,主要影响年轻人。尽管疾病的确切病因仍不清楚,但很明显,代谢组的改变对此过程有贡献。因此,定义一个可靠的、具有疾病特异性的代谢组具有作为 MS 的诊断和治疗策略的巨大潜力。在这里,我们提供了一项旨在确定代谢组学在 MS 中的作用的研究概述。这些研究为疾病病理生理学和代谢途径对该过程的贡献提供了新的见解,确定了指示治疗反应的独特标志物,并在 MS 的细胞和动物模型中证明了类药代谢物的治疗效果。总的来说,MS 及其临床前模型中常见的失调途径包括涉及α-亚麻酸途径的脂质代谢、核苷酸代谢、氨基酸代谢、三羧酸循环、D-鸟氨酸和 D-精氨酸途径,这些途径在信号转导和能量供应方面发挥着共同作用。代谢组学研究表明,对 MS 患者样本进行代谢谱分析可能会发现生物标志物,从而增进我们对疾病发病机制和进展的理解,减少诊断中的延迟和错误,监测疾病进程,并发现更好的药物靶点,所有这些都将改善早期治疗干预措施并提高对这些治疗的反应评估。