Exploring dysregulated miRNAs in ALS: implications for disease pathogenesis and early diagnosis.

IF 2.7 4区医学 Q2 CLINICAL NEUROLOGY Neurological Sciences Pub Date : 2024-11-21 DOI:10.1007/s10072-024-07840-x

Dipan Maity, Ravinder K Kaundal

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Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor neuron degeneration, leading to muscle weakness and paralysis, with no effective treatments available. Early diagnosis could slow disease progression and optimize treatment. MicroRNAs (miRNAs) are being investigated as potential biomarkers due to their regulatory roles in cellular processes and stability in biofluids. However, variability across studies complicates their diagnostic utility in ALS. This study aims to identify significantly dysregulated miRNAs in ALS through meta-analysis to elucidate disease mechanisms and improve diagnostic strategies.

Methods: We systematically searched PubMed, Google Scholar, and the Cochrane Library, following predefined inclusion and exclusion criteria. The primary effect measure was the standardized mean difference (SMD) with a 95% confidence interval, analyzed using a random-effects model. Additionally, we used network pharmacology to examine the targets of dysregulated miRNAs and their roles in ALS pathology.

Results: Analysing 34 studies, we found significant upregulation of hsa-miR-206, hsa-miR-133b, hsa-miR-23a, and hsa-miR-338-3p, and significant downregulation of hsa-miR-218, hsa-miR-21-5p, and hsa-let-7b-5p in ALS patients. These miRNAs are involved in ALS pathophysiology, including stress granule formation, nuclear pore complex, SMCR8 and Sig1R dysfunction, histone methyltransferase complex alterations, and MAPK signaling perturbation, highlighting their critical role in ALS progression.

Conclusion: This study identifies several dysregulated miRNAs in ALS patients, offering insights into their role in the disease and potential as diagnostic biomarkers. These findings enhance our understanding of ALS mechanisms and may inform future diagnostic strategies. Validating these results and exploring miRNA-based interventions are crucial for improving ALS diagnosis and treatment outcomes.

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探索 ALS 中失调的 miRNAs：对疾病发病机制和早期诊断的影响。

背景：肌萎缩侧索硬化症（ALS）是一种以运动神经元变性为特征的进行性神经退行性疾病，可导致肌肉无力和瘫痪，目前尚无有效的治疗方法。早期诊断可延缓疾病的进展并优化治疗。由于微小核糖核酸（miRNA）在细胞过程中的调控作用和在生物流体中的稳定性，它们正被研究作为潜在的生物标志物。然而，不同研究之间的差异使其在 ALS 诊断中的作用变得复杂。本研究旨在通过荟萃分析确定 ALS 中明显失调的 miRNA，以阐明疾病机制并改进诊断策略：我们按照预先确定的纳入和排除标准，系统地检索了 PubMed、谷歌学术和 Cochrane 图书馆。主要效应指标为标准化平均差（SMD）及 95% 置信区间，并采用随机效应模型进行分析。此外，我们还利用网络药理学研究了失调 miRNAs 的靶标及其在 ALS 病理学中的作用：结果：通过分析 34 项研究，我们发现在 ALS 患者中，hsa-miR-206、hsa-miR-133b、hsa-miR-23a 和 hsa-miR-338-3p 明显上调，而 hsa-miR-218、hsa-miR-21-5p 和 hsa-let-7b-5p 则明显下调。这些miRNA参与了ALS的病理生理学过程，包括应激颗粒形成、核孔复合体、SMCR8和Sig1R功能障碍、组蛋白甲基转移酶复合体改变和MAPK信号扰动，凸显了它们在ALS进展中的关键作用：这项研究发现了 ALS 患者体内几种失调的 miRNAs，深入揭示了它们在该病中的作用以及作为诊断生物标志物的潜力。这些发现加深了我们对 ALS 机制的了解，并可能为未来的诊断策略提供依据。验证这些结果并探索基于 miRNA 的干预措施对改善 ALS 诊断和治疗效果至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurological Sciences 医学-临床神经学

CiteScore

6.10

自引率

3.00%

发文量

743

审稿时长

4 months

期刊介绍： Neurological Sciences is intended to provide a medium for the communication of results and ideas in the field of neuroscience. The journal welcomes contributions in both the basic and clinical aspects of the neurosciences. The official language of the journal is English. Reports are published in the form of original articles, short communications, editorials, reviews and letters to the editor. Original articles present the results of experimental or clinical studies in the neurosciences, while short communications are succinct reports permitting the rapid publication of novel results. Original contributions may be submitted for the special sections History of Neurology, Health Care and Neurological Digressions - a forum for cultural topics related to the neurosciences. The journal also publishes correspondence book reviews, meeting reports and announcements.