背景:肌萎缩侧索硬化症(ALS)是一种破坏性的神经退行性疾病,其发病机制在很大程度上未知,并且没有有效的治愈方法。据信,有几个,不是相互排斥的机制有助于这种疾病的发病机制和进展,包括,其中,氧化应激升高,兴奋毒性,神经炎症增加,和蛋白质聚集。晚期糖基化终产物受体(RAGE)是免疫球蛋白超家族的一部分;它被认为参与了ALS的发病机理。
目的:我们以前对ALS的研究表明,RAGE可能是ALS的主要参与者之一,自身作用,并与其氧化应激和促炎配体协同作用,例如高级糖基化终产物(AGEs)或高级氧化蛋白产物(AOPPs)。在这项研究中,根据我们之前的结果,我们的目标是建立可溶性RAGE的血液水平,ALS患者的AGE和AOPP。
方法:研究中使用了46份编码和匿名的来自ALS患者和非神经对照的剩余血浆样本。愤怒的血浆水平,使用酶联免疫吸附测定(ELISA)市售试剂盒测量AGE和AOPP。使用单向非参数方差分析(ANOVA)和Kruskal-Wallis事后检验进行数据的统计评估。
结果:我们的结果显示可溶性RAGE水平下降,与ALS患者血液样本中AGEs和AOPP水平的增加同时,表明RAGE的神经保护形式丧失,并且在疾病的早期阶段同时增加AGE和AOPP的产生和摄取。
结论:从我们的研究中获得的结果表明,对RAGE的进一步纵向研究,年龄和AOPP水平将是有益的,概述RAGE和它的配体水平之间的动态随着疾病的进展,并使它们成为有价值的诊断工具和潜在的治疗目标。
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with largely unknown pathogenesis and no effective cure. It is believed that several, not mutually exclusive mechanisms contribute to the pathogenesis and progression of this disease, including, among others, elevated oxidative stress, excitotoxicity, increased neuroinflammation, and protein aggregation. Receptor for advanced glycation end products (RAGE) is a part of immunoglobulin superfamily; it is believed to participate in ALS pathogenesis.
OBJECTIVE: Our previous studies on ALS demonstrated that RAGE is likely one of the key players in ALS, acting on its own and in tandem with its oxidative stress and pro-inflammatory ligands, such as advanced glycation end products (AGEs) or advanced oxidation protein products (AOPPs). In this study, based on our previous results, we aimed to establish blood levels of soluble RAGE, AGE and AOPP in ALS patients.
METHODS: Forty-six coded and anonymized surplus plasma samples from ALS patients and non-neurological control were used in the study. The plasma levels of RAGE, AGE and AOPP were measured using enzyme-linked immunosorbent assay (ELISA) commercially available kits. Statistical evaluation of data was performed using one-way non-parametric analysis of variance (ANOVA) with Kruskal-Wallis post hoc test.
RESULTS: Our results revealed a decline in soluble RAGE level, concurrent with an increase in the levels of AGEs and AOPPs in blood samples from ALS patients, signifying a loss of neuroprotective form of RAGE and a simultaneous increase in AGE and AOPP production and uptake at the early stage of the disease.
CONCLUSIONS: The results obtained from our study indicate that further longitudinal study of RAGE, AGE and AOPP levels would be beneficial, outlining the dynamics between RAGE and its ligand levels as the disease progresses, and making them valuable diagnostic tools and potential therapeutic targets.