Nakazato Tomoko, Kanai Kazuaki, Kataura Tetsushi, Nojiri Shuko, Hattori Nobutaka, Saiki Shinji
Department of Neurology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Department of Neurology, Fukushima Medical University, Fukushima, Japan.
Sci Rep. 2022 Jun 1;12(1):9155. doi: 10.1038/s41598-022-13397-6.
Although various body fluid biomarkers for amyotrophic lateral sclerosis (ALS) have been reported, no biomarkers specifically reflecting abnormalities in axonal excitability indices have currently been established. Capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography time-of-flight mass spectrometry were used to perform a comprehensive metabolome analysis of plasma from seven ALS patients and 20 controls, and correlation analysis with disease phenotypes was then performed in 22 other ALS patients. Additionally, electrophysiological studies of motor nerve axonal excitability were performed in all ALS patients. In the ALS and control groups, levels of various metabolites directly associated with skeletal muscle metabolism, such as those involved in fatty acid β-oxidation and the creatine pathway, were detected. Receiver operating characteristic curve analysis of the top four metabolites (ribose-5-phosphate, N6-acetyllysine, dyphylline, 3-methoxytyrosine) showed high diagnostic accuracy (area under the curve = 0.971) in the ALS group compared with the control group. Furthermore, hierarchical cluster analysis revealed that taurine levels were correlated with the strength-duration time constant, an axonal excitability indicator established to predict survival. No significant effects of diabetes mellitus and treatment (Riluzole and Edaravone) on this relationship were detected in the study. Therefore, plasma taurine is a potential novel axonal excitability-translatable biomarker for ALS.
尽管已经报道了多种用于肌萎缩侧索硬化症（ALS）的体液生物标志物，但目前尚未建立专门反映轴突兴奋性指标异常的生物标志物。采用毛细管电泳飞行时间质谱和液相色谱飞行时间质谱对7例ALS患者和20例对照者的血浆进行综合代谢组分析，然后对另外22例ALS患者进行与疾病表型的相关性分析。此外，对所有ALS患者进行运动神经轴突兴奋性的电生理研究。在ALS组和对照组中，检测到了与骨骼肌代谢直接相关的各种代谢物水平，如参与脂肪酸β氧化和肌酸途径的代谢物。对前四种代谢物（5-磷酸核糖、N6-乙酰赖氨酸、二羟丙茶碱、3-甲氧基酪氨酸）的受试者工作特征曲线分析显示，与对照组相比，ALS组具有较高的诊断准确性（曲线下面积=0.971）。此外，层次聚类分析显示，牛磺酸水平与强度-时间常数相关，强度-时间常数是一种用于预测生存的轴突兴奋性指标。在该研究中未检测到糖尿病和治疗（利鲁唑和依达拉奉）对这种关系的显著影响。因此，血浆牛磺酸是一种潜在的新型可转化为轴突兴奋性的ALS生物标志物。
