MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients.
MAPKAPK2, a potential dynamic network biomarker of α-synuclein prior to its aggregation in PD patients.
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MAPKAPK2是PD患者α-突触核蛋白聚集前的潜在动态网络生物标志物。
DOI：
10.1038/s41531-023-00479-z
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发表时间：
2023-03-16
影响因子：
8.7
通讯作者：
Ling, Fei
中科院分区：
文献类型：
--
作者：
Zhong, Zhenggang;Li, Jiabao;Zhong, Jiayuan;Huang, Yilin;Hu, Jiaqi;Zhang, Piao;Zhang, Baowen;Jin, Yabin;Luo, Wei;Liu, Rui;Zhang, Yuhu;Ling, Fei
帕金森病（PD）的重要病理特征之一是α-突触核蛋白（α-Syn）在黑质的病理聚集。防止α-Syn聚集已成为治疗PD的潜在策略。然而，α-Syn聚集的分子机制尚不清楚。在本研究中，我们利用动态网络生物标志物（DNB）方法，首先基于SH-SY5Y细胞模型确定了α-Syn发生病理聚集的关键时间点，并发现DNB基因编码调节差异表达的靶基因的转录因子。有趣的是，我们发现这些DNB基因及其邻近基因在细胞衰老途径中显着富集，因此提出DNB基因HSF1和MAPKAPK2调节邻近基因SERPINE1的表达。值得注意的是，从黑质、前额皮质和外周血样本获得的基因表达综合（GEO）数据中，PD患者中MAPKAPK2的表达水平显着高于健康人，这表明MAPKAPK2有潜力作为与α-Syn病理聚集相关的疾病（例如PD）的早期诊断生物标志物。这些发现为 α-Syn 病理聚集的机制提供了新的见解。
One of the important pathological features of Parkinson’s disease (PD) is the pathological aggregation of α-synuclein (α-Syn) in the substantia nigra. Preventing the aggregation of α-Syn has become a potential strategy for treating PD. However, the molecular mechanism of α-Syn aggregation is unclear. In this study, using the dynamic network biomarker (DNB) method, we first identified the critical time point when α-Syn undergoes pathological aggregation based on a SH-SY5Y cell model and found that DNB genes encode transcription factors that regulated target genes that were differentially expressed. Interestingly, we found that these DNB genes and their neighbouring genes were significantly enriched in the cellular senescence pathway and thus proposed that the DNB genes HSF1 and MAPKAPK2 regulate the expression of the neighbouring gene SERPINE1. Notably, in Gene Expression Omnibus (GEO) data obtained from substantia nigra, prefrontal cortex and peripheral blood samples, the expression level of MAPKAPK2 was significantly higher in PD patients than in healthy people, suggesting that MAPKAPK2 has potential as an early diagnostic biomarker of diseases related to pathological aggregation of α-Syn, such as PD. These findings provide new insights into the mechanisms underlying the pathological aggregation of α-Syn.
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影响因子：
6
作者：
Han C;Zhong J;Zhang Q;Hu J;Liu R;Liu H;Mo Z;Chen P;Ling F
通讯作者：
Ling F
单细胞转录组学揭示成熟 B 细胞中的 DHX9 作为 CRC 淋巴结转移前的动态网络生物标志物
DOI：
10.1016/j.omto.2021.06.004
发表时间：
2021-09-24
期刊：
Molecular therapy oncolytics
影响因子：
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作者：
Liu H;Zhong J;Hu J;Han C;Li R;Yao X;Liu S;Chen P;Liu R;Ling F
通讯作者：
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影响因子：
18.9
作者：
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通讯作者：
Chen, Luonan
影响因子：
2.8
作者：
Liangliang, Xu;Yonghui, Hou;Jiangying, Zou
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通讯作者：
Je, Hyunsoo Shawn