LncRNA-T199678 Mitigates α-Synuclein-Induced Dopaminergic Neuron Injury via miR-101-3p.
LncRNA-T199678 Mitigates α-Synuclein-Induced Dopaminergic Neuron Injury via miR-101-3p.
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LncRNA-T199678 通过 miR-101-3p 减轻 α-突触核蛋白诱导的多巴胺能神经元损伤
DOI：
10.3389/fnagi.2020.599246
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发表时间：
2020
影响因子：
4.8
通讯作者：
Tao EX
中科院分区：
文献类型：
--
作者：
Bu LL;Xie YY;Lin DY;Chen Y;Jing XN;Liang YR;Peng SD;Huang KX;Tao EX
帕金森病（Parkinson's disease，PD）是第二常见的神经退行性疾病，其特征是多巴胺能神经元死亡和黑质（substantia nigra，SN）中α-突触核蛋白（α-synuclein，α-Syn）的异常积聚和聚集。虽然α-Syn的异常积累可以单独促进和加速PD的进展，但其潜在的分子机制尚不清楚。越来越多的证据表明，长链非编码RNA（lncRNA）的异常表达在PD中起着重要作用。我们前期的研究通过基因芯片分析发现外源性α-Syn诱导SH-SY 5 Y细胞中lncRNA-T199678表达下调。提示lncRNA-T199678可能在PD的发病机制中具有潜在的病理作用。本研究旨在探讨lncRNA-T199678对α-Syn诱导的多巴胺能神经元损伤的影响。过表达lncRNA-T199678可通过调节氧化应激、细胞周期和凋亡减轻α-Syn诱导的神经元损伤。研究表明lncRNA可以通过调控下游microRNA（miRNA）来调控转录后基因的表达。为了发现lncRNA-T199678的下游分子靶标，以下实验发现miR-101- 3 p是lncRNA-T199678的潜在靶标。进一步的研究表明，lncRNA-T199678的上调可通过miR-101- 3 p减轻α-Syn诱导的SH-SY 5 Y细胞神经元损伤，lncRNA-T199678参与了α-Syn诱导的细胞内氧化应激、细胞周期紊乱和细胞凋亡。总之，lncRNA-T199678通过靶向miR-101- 3 p减轻α-Syn诱导的多巴胺能神经元损伤，这有助于促进PD。我们的研究结果强调了lncRNA-T199678在减轻PD中多巴胺能神经元损伤中的作用，并揭示了PD的新分子靶点。
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by dopaminergic neuron death and the abnormal accumulation and aggregation of α-synuclein (α-Syn) in the substantia nigra (SN). Although the abnormal accumulation of α-Syn can solely promote and accelerate the progress of PD, the underlying molecular mechanisms remain unknown. Mounting evidence confirms that the abnormal expression of long non-coding RNA (lncRNA) plays an important role in PD. Our previous study found that exogenous α-Syn induced the downregulation of lncRNA-T199678 in SH-SY5Y cells via a gene microarray analysis. This finding suggested that lncRNA-T199678 might have a potential pathological role in the pathogenesis of PD. This study aimed to explore the influence of lncRNA-T199678 on α-Syn-induced dopaminergic neuron injury. Overexpression of lncRNA-T199678 ameliorated the neuron injury induced by α-Syn via regulating oxidative stress, cell cycle, and apoptosis. Studies indicate lncRNAs could regulate posttranscriptional gene expression via regulating the downstream microRNA (miRNA). To discover the downstream molecular target of lncRNA-T199678, the following experiment found out that miR-101-3p was a potential target for lncRNA-T199678. Further study showed that the upregulation of lncRNA-T199678 reduced α-Syn-induced neuronal damage through miR-101-3p in SH-SY5Y cells and lncRNA-T199678 was responsible for the α-Syn-induced intracellular oxidative stress, dysfunction of the cell cycle, and apoptosis. All in all, lncRNA-T199678 mitigated the α-Syn-induced dopaminergic neuron injury via targeting miR-101-3p, which contributed to promote PD. Our results highlighted the role of lncRNA-T199678 in mitigating dopaminergic neuron injury in PD and revealed a new molecular target for PD.
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DOI：
10.1073/pnas.0611671104
发表时间：
2007-02-27
影响因子：
11.1
作者：
Hoeglinger, Guenter U.;Breunig, Joshua J.;Hunot, Stephane
通讯作者：
Hunot, Stephane
影响因子：
168.9
作者：
Kalia, Lorraine V.;Lang, Anthony E.
通讯作者：
Lang, Anthony E.
影响因子：
3.7
作者：
Lin, Qiuyu;Hou, Sen;Lin, Yingjie
通讯作者：
Lin, Yingjie
影响因子：
5.3
作者：
Fragkouli A;Doxakis E
通讯作者：
Doxakis E
影响因子：
81.5
作者：
Poewe, Werner;Seppi, Klaus;Lang, Anthony E.
通讯作者：
Lang, Anthony E.