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SOMAscan 蛋白质组学在肌萎缩侧索硬化症患者中鉴定出新型血浆蛋白。

SOMAscan Proteomics Identifies Novel Plasma Proteins in Amyotrophic Lateral Sclerosis Patients.

机构信息

S.C. Neuroscienze, Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d'Aosta, 10154 Turin, Italy.

Cancer Genomics Laboratory, Fondazione Edo ed Elvo Tempia, 13900 Biella, Italy.

出版信息

Int J Mol Sci. 2023 Jan 18;24(3):1899. doi: 10.3390/ijms24031899.

Abstract

Amyotrophic lateral sclerosis (ALS) is a complex disease characterized by the interplay of genetic and environmental factors for which, despite decades of intense research, diagnosis remains rather delayed, and most therapeutic options fail. Therefore, unravelling other potential pathogenetic mechanisms and searching for reliable markers are high priorities. In the present study, we employ the SOMAscan assay, an aptamer-based proteomic technology, to determine the circulating proteomic profile of ALS patients. The expression levels of ~1300 proteins were assessed in plasma, and 42 proteins with statistically significant differential expression between ALS patients and healthy controls were identified. Among these, four were upregulated proteins, Thymus- and activation-regulated chemokine, metalloproteinase inhibitor 3 and nidogen 1 and 2 were selected and validated by enzyme-linked immunosorbent assays in an overlapping cohort of patients. Following statistical analyses, different expression patterns of these proteins were observed in the familial and sporadic ALS patients. The proteins identified in this study might provide insight into ALS pathogenesis and represent potential candidates to develop novel targeted therapies.

摘要

肌萎缩侧索硬化症(ALS)是一种复杂的疾病,其特征是遗传和环境因素相互作用。尽管经过数十年的深入研究,其诊断仍然相当滞后,而且大多数治疗方法都失败了。因此,揭示其他潜在的发病机制并寻找可靠的标志物是当务之急。在本研究中,我们采用 SOMAscan 检测法,一种基于适体的蛋白质组学技术,来确定肌萎缩侧索硬化症患者的循环蛋白质组特征。我们评估了血浆中约 1300 种蛋白质的表达水平,并确定了 ALS 患者与健康对照组之间具有统计学显著差异的 42 种蛋白质。其中,有 4 种是上调蛋白,然后通过酶联免疫吸附测定法在一个重叠的患者队列中对胸腺激活调节趋化因子、金属蛋白酶抑制剂 3 以及巢蛋白 1 和 2 进行了选择和验证。经过统计学分析,在家族性和散发性肌萎缩侧索硬化症患者中观察到这些蛋白的不同表达模式。本研究中鉴定的蛋白可能为肌萎缩侧索硬化症的发病机制提供了深入的了解,并代表了开发新型靶向治疗方法的潜在候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d3f/9916400/503c37306ee5/ijms-24-01899-g001.jpg

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