Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q.
Apoptosis signal-regulating kinase 1 mediates striatal degeneration via the regulation of C1q.
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DOI：
10.1038/srep18840
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发表时间：
2016-01-05
影响因子：
4.6
通讯作者：
Kim GW
中科院分区：
文献类型：
--
作者：
Cho KJ;Cheon SY;Kim GW
细胞凋亡信号调节激酶-1 (ASK1) 是细胞死亡途径中的早期信号元件，据推测参与神经退行性疾病的病理学。 3-硝基丙酸（3-NP）的全身给药促进选择性纹状体病变的发展。然而，目前尚不清楚特定神经元是否选择性地靶向 3-NP 注入的纹状体变性。最近，有人提出补体介导的突触消除可能在神经退行性疾病的病理学中异常重新激活。我们假设 ASK1 参与纹状体星形胶质细胞的重新激活；反应性星形胶质细胞分泌对神经元有害的分子；纹状体神经元更容易受到这些因素的影响。我们的结果表明，3-NP 常规和长期输注后，纹状体星形胶质细胞被重新激活，ASK1 水平增加。反应性纹状体星形胶质细胞增加 TGF-β 的程度与皮质和纹状体不同。 ASK1可能参与星形胶质细胞TGF-β的调节，并且在空间和时间上与C1q水平相关，而且在进展性纹状体神经元损失的早期阶段。最终，本研究表明 ASK1 介导 3-NP 毒性并通过星形胶质细胞 TGF-β 调节 C1q 水平。它还可能表明 C1q 水平可能是代表神经退行性疾病在出现行为障碍之前进展的预测标记的替代。
Apoptosis signal-regulating kinase-1 (ASK1), an early signaling element in the cell death pathway, has been hypothesized to participate in the pathology of neurodegenerative diseases. The systemic administration of 3-nitropropionic acid (3-NP) facilitates the development of selective striatal lesions. However, it remains unclear whether specific neurons are selectively targeted in 3-NP-infused striatal degeneration. Recently, it has been proposed that complement-mediated synapse elimination may be reactivated aberrantly in the pathology of neurodegenerative diseases. We hypothesized that ASK1 is involved in striatal astrocyte reactivation; reactive astrocyte secretes molecules detrimental to neuron; and striatal neurons are more susceptible to these factors. Our results indicate that striatal astrocyte is reactivated and ASK1 level increases after 3-NP general and chronic infusion. Reactive striatal astrocyte increases TGF-beta differentially to cortex and striatum. ASK1 may be involved in regulation of astrocyte TGF-beta and it is linked to the C1q level in spatial and temporal, and moreover in the earlier stage of progressing striatal neuronal loss. Conclusively the present study suggests that ASK1 mediates 3-NP toxicity and regulates C1q level through the astrocyte TGF-beta. And also it may suggest that C1q level may be a surrogate of prediction marker representing neurodegenerative disease progress before developing behavioral impairment.