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Reelin 减轻间充质干细胞衰老并降低帕金森病体外模型中病理性 α-突触核蛋白的表达。

Reelin Alleviates Mesenchymal Stem Cell Senescence and Reduces Pathological α-Synuclein Expression in an In Vitro Model of Parkinson's Disease.

机构信息

Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul 03722, Korea.

Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea.

出版信息

Genes (Basel). 2021 Jul 13;12(7):1066. doi: 10.3390/genes12071066.

DOI:10.3390/genes12071066
PMID:34356083
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8308051/
Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. The mechanisms underlying PD remain to be fully elucidated, and research into treatments for this condition is ongoing. Recent advances in genetic research have shed light on the mechanisms underlying PD. In this study, we used PD and control mesenchymal stem cells (MSCs) obtained from adipose tissues to confirm the differences between groups at the cellular and molecular levels. The results revealed that in PD MSCs, cell viability was clearly lower, and the rate of cell senescence was higher compared to the controls. Next, to compare the gene expression in PD and control cells, transcriptome analysis was performed. Genes in pathways, including extracellular matrix (ECM) receptor interaction, P53 signaling, and focal adhesion, were down-regulated in PD. Among genes related to ECM receptor interaction, gene expression was markedly decreased in PD cells; however, after being treated with recombinant Reelin protein, a significant increase in cell viability and a decrease in α-Synuclein aggregation and cell senescence were observed. In conclusion, Reelin affects PD by positively influencing the cell characteristics. Our findings will facilitate research into new treatments for PD.

摘要

帕金森病(PD)是最常见的神经退行性疾病之一。PD 的发病机制尚未完全阐明,目前仍在研究该疾病的治疗方法。遗传研究的最新进展揭示了 PD 的发病机制。在这项研究中,我们使用来自脂肪组织的 PD 和对照间充质干细胞(MSCs)来确认细胞和分子水平上两组之间的差异。结果表明,与对照组相比,PD-MSCs 的细胞活力明显更低,细胞衰老率更高。接下来,为了比较 PD 和对照细胞中的基因表达,进行了转录组分析。在 PD 中,包括细胞外基质(ECM)受体相互作用、P53 信号和黏着斑在内的通路中的基因表达下调。在与 ECM 受体相互作用相关的基因中, 基因在 PD 细胞中的表达明显降低;然而,在用重组 Reelin 蛋白处理后,观察到细胞活力显著增加,α-突触核蛋白聚集和细胞衰老减少。总之,Reelin 通过积极影响细胞特征来影响 PD。我们的研究结果将有助于研究 PD 的新治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/1f509a8e65e2/genes-12-01066-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/2f6b7738094a/genes-12-01066-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/b35d5e512aea/genes-12-01066-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/0740b51f7b18/genes-12-01066-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/f339f70f22ab/genes-12-01066-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/83a488ef5436/genes-12-01066-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/2715fb603662/genes-12-01066-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/1f509a8e65e2/genes-12-01066-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/2f6b7738094a/genes-12-01066-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/b35d5e512aea/genes-12-01066-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/0740b51f7b18/genes-12-01066-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/f339f70f22ab/genes-12-01066-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/83a488ef5436/genes-12-01066-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/2715fb603662/genes-12-01066-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2417/8308051/1f509a8e65e2/genes-12-01066-g007.jpg

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