Instituto de Fisiologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
ToxOmics, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal.
Mol Neurobiol. 2023 Dec;60(12):7104-7117. doi: 10.1007/s12035-023-03520-7. Epub 2023 Aug 2.
Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that affects nerve cells in the brain and spinal cord, causing loss of muscle control, muscle atrophy and in later stages, death. Diagnosis has an average delay of 1 year after symptoms onset, which impairs early management. The identification of a specific disease biomarker could help decrease the diagnostic delay. MicroRNA (miRNA) expression levels have been proposed as ALS biomarkers, and altered function has been reported in ALS pathogenesis. The aim of this study was to assess the differential expression of plasma miRNAs in ALS patients and two control populations (healthy controls and ALS-mimic disorders). For that, 16 samples from each group were pooled, and then 1008 miRNAs were assessed through reverse transcription-quantitative polymerase chain reaction (RT-qPCR). From these, ten candidate miRNAs were selected and validated in 35 ALS patients, 16 ALS-mimic disorders controls and 15 healthy controls. We also assessed the same miRNAs in two different time points of disease progression. Although we were unable to determine a miRNA signature to use as disease or condition marker, we found that miR-7-2-3p, miR-26a-1-3p, miR-224-5p and miR-206 are good study candidates to understand the pathophysiology of ALS.
肌萎缩侧索硬化症(ALS)是一种进行性运动神经元疾病,影响大脑和脊髓中的神经细胞,导致肌肉控制丧失、肌肉萎缩,在后期导致死亡。症状出现后,平均需要 1 年才能确诊,这会影响早期治疗。如果能识别出特定的疾病生物标志物,可能有助于缩短诊断时间。有人提出 microRNA(miRNA)表达水平可作为 ALS 生物标志物,并且在 ALS 发病机制中已经报道了功能改变。本研究旨在评估 ALS 患者与两个对照组(健康对照和 ALS 模拟疾病)的血浆 miRNA 的差异表达。为此,将每组的 16 个样本混合,然后通过逆转录定量聚合酶链反应(RT-qPCR)评估 1008 个 miRNA。从中选择了十个候选 miRNA,并在 35 名 ALS 患者、16 名 ALS 模拟疾病对照和 15 名健康对照中进行验证。我们还在疾病进展的两个不同时间点评估了相同的 miRNA。尽管我们无法确定可用于疾病或病症标记的 miRNA 特征,但我们发现 miR-7-2-3p、miR-26a-1-3p、miR-224-5p 和 miR-206 是研究 ALS 病理生理学的良好候选者。