PDF(Pubmed)
Abstract：
Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease type of motor neuron disorder characterized by degeneration of the upper and lower motor neurons resulting in dysfunction of the somatic muscles of the body. The ALS condition is manifested in progressive skeletal muscle atrophy and spasticity. It leads to death, mostly due to respiratory failure. Within the pathophysiology of the disease, muscle energy metabolism seems to be an important part. In our study, we used blood plasma from 25 patients with ALS diagnosed by definitive El Escorial criteria according to ALSFR-R (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale) criteria and 25 age and sex-matched subjects. Aside from standard clinical biochemical parameters, we used the NMR (nuclear magnetic resonance) metabolomics approach to determine relative plasma levels of metabolites. We observed a decrease in total protein level in blood; however, despite accelerated skeletal muscle catabolism characteristic for ALS patients, we did not detect changes in plasma levels of essential amino acids. When focused on alterations in energy metabolism within muscle, compromised creatine uptake was accompanied by decreased plasma creatinine. We did not observe changes in plasma levels of BCAAs (branched chain amino acids; leucine, isoleucine, valine); however, the observed decrease in plasma levels of all three BCKAs (branched chain alpha-keto acids derived from BCAAs) suggests enhanced utilization of BCKAs as energy substrate. Glutamine, found to be increased in blood plasma in ALS patients, besides serving for ammonia detoxification, could also be considered a potential TCA (tricarboxylic acid) cycle contributor in times of decreased pyruvate utilization. When analyzing the data by using a cross-validated Random Forest algorithm, it finished with an AUC of 0.92, oob error of 8%, and an MCC (Matthew\'s correlation coefficient) of 0.84 when relative plasma levels of metabolites were used as input variables. Although the discriminatory power of the system used was promising, additional features are needed to create a robust discriminatory model.
摘要：
肌萎缩侧索硬化症（ALS）是一种致命的神经肌肉疾病类型的运动神经元疾病，其特征在于上运动神经元和下运动神经元的变性，导致身体的躯体肌肉功能障碍。ALS病症表现为进行性骨骼肌萎缩和痉挛。它导致死亡，主要是由于呼吸衰竭。在疾病的病理生理学中，肌肉能量代谢似乎是一个重要的部分。在我们的研究中,我们使用根据ALSFR-R(经修订的肌萎缩侧索硬化功能评定量表)标准通过明确的ElEscorial标准诊断的25例ALS患者和25例年龄和性别匹配的受试者的血浆.除了标准的临床生化参数,我们使用NMR(核磁共振)代谢组学方法来确定代谢物的相对血浆水平.我们观察到血液中总蛋白质水平下降;然而，尽管ALS患者的骨骼肌分解代谢加速，我们未检测到血浆必需氨基酸水平的变化.当关注肌肉内能量代谢的改变时，肌酸摄取受损伴有血浆肌酐下降。我们没有观察到血浆BCAAs（支链氨基酸；亮氨酸，异亮氨酸,缬氨酸)；然而，观察到的所有三种BCKA（衍生自BCAAs的支链α-酮酸）的血浆水平降低表明BCKA作为能量底物的利用率提高。谷氨酰胺,发现ALS患者的血浆增加，除了用于氨解毒，在丙酮酸利用率降低的时候，也可以被认为是潜在的TCA（三羧酸）循环贡献者。使用交叉验证的随机森林算法分析数据时，它的AUC为0.92，oob误差为8%，当代谢物的相对血浆水平用作输入变量时，MCC（马修相关系数）为0.84。尽管所使用的系统的歧视性是有希望的，需要额外的功能来创建一个强大的歧视性模型。
