Characterization of tRNA-derived fragments in the small neuron-derived extracellular vesicles of Alzheimer’s disease patients

IF 2.7 4区医学 Q3 NEUROSCIENCES

Brain Research Pub Date : 2025-05-26 DOI:10.1016/j.brainres.2025.149730

Burak I. Arioz , Leman Binokay , Bora Tastan , Bilgesu Genc , Aysen Cotuk , Erdinç Dursun , Duygu Gezen-Ak , Hasmet Hanagası , I.Hakan Gurvit , Basar Bilgic , Alper Bagriyanik , Gökhan Karakülah , Görsev G Yener , Sermin Genc

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引用次数: 0

Abstract

Introduction

Alzheimer’s disease (AD) is a progressive neurological disorder characterized by memory loss and cognitive impairment. The development of neurofibrillary tangles and amyloid plaques are pathological hallmarks of the disease. Molecular mechanisms underlying AD are multifaceted, extracellular vesicles contribute disease pathogenesis via cargo molecules such as DNA, protein, RNA and non-coding RNAs. tRNA-derived fragments (tRFs) are small non-coding RNAs with regulatory functions and their alterations have been demonstrated in various diseases. In this study, we aimed to investigate peripherally altered tRFs in small neuron-derived extracellular vesicles (sNDEVs) from AD patients.

Method

83 AD patients and 39 healthy controls were enrolled to study. After total sEVs isolation with ultracentrifugation, sNDEVs were enriched with CD171. EVs were characterized using Western blot, nanoparticle tracking analysis (NTA), and STEM. We utilized next-generation sequencing to analyze the expression profiles of tRFs in sNDEVs from AD patients compared to healthy controls. For the Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, we employed the ShinyGO web tool. The alterations of two differentially expressed tRNA fragments in the sNDEVs of AD patients, were confirmed using the RT-qPCR method.

Result

In our study we found that three tRFs were significantly upregulated, and 10 tRFs were significantly downregulated. Then, we confirmed the upregulation of tRF-20-1HPSR9O9 and the downregulation of tRF-33-RM7KYUPRENRHD2 on a larger population with the RT-qPCR method. In the KEGG and GO analyses using targets of detected tRFs, we found significant terms related to brain and neurons, such as neuron projection morphogenesis, neuron differentiation, long-term depression and glutamatergic synapse.

Conclusion

Our study suggests that tRFs in sNDEVs of AD patients differ from controls and the role of these tRFs in disease pathogenesis be investigated in further studies.

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阿尔茨海默病患者小神经元源性细胞外囊泡中trna来源片段的表征

阿尔茨海默病（AD）是一种以记忆丧失和认知障碍为特征的进行性神经系统疾病。神经原纤维缠结和淀粉样斑块的发展是该病的病理标志。AD的分子机制是多方面的，细胞外囊泡通过货物分子如DNA、蛋白质、RNA和非编码RNA参与疾病的发病机制。trna衍生片段（trf）是具有调节功能的小非编码rna，其改变已在多种疾病中得到证实。在这项研究中，我们旨在研究AD患者的小神经元源性细胞外囊泡（sNDEVs）的外周改变的tRFs。方法83例AD患者和39例健康对照者作为研究对象。全sev经超离心分离后，sNDEVs富集CD171。采用Western blot、纳米颗粒跟踪分析（NTA）和STEM对电动汽车进行表征。我们利用下一代测序分析了AD患者sNDEVs中tRFs的表达谱，并与健康对照进行了比较。对于基因本体（GO）富集和京都基因与基因组百科全书（KEGG）通路分析，我们使用了ShinyGO web工具。采用RT-qPCR方法证实了AD患者sNDEVs中两个差异表达的tRNA片段的改变。结果在我们的研究中，我们发现3个tRFs显著上调，10个tRFs显著下调。然后，我们用RT-qPCR方法在更大的人群中证实了tRF-20-1HPSR9O9的上调和tRF-33-RM7KYUPRENRHD2的下调。在使用检测到的tRFs靶标的KEGG和GO分析中，我们发现了与脑和神经元相关的重要术语，如神经元投射形态发生、神经元分化、长期抑制和谷氨酸能突触。结论AD患者sNDEVs中tRFs与对照组存在差异，这些tRFs在疾病发病机制中的作用有待进一步研究。

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

Brain Research 医学-神经科学

CiteScore

5.90

自引率

3.40%

发文量

268

审稿时长

47 days

期刊介绍： An international multidisciplinary journal devoted to fundamental research in the brain sciences. Brain Research publishes papers reporting interdisciplinary investigations of nervous system structure and function that are of general interest to the international community of neuroscientists. As is evident from the journals name, its scope is broad, ranging from cellular and molecular studies through systems neuroscience, cognition and disease. Invited reviews are also published; suggestions for and inquiries about potential reviews are welcomed. With the appearance of the final issue of the 2011 subscription, Vol. 67/1-2 (24 June 2011), Brain Research Reviews has ceased publication as a distinct journal separate from Brain Research. Review articles accepted for Brain Research are now published in that journal.