Meclizine-induced enhanced glycolysis is neuroprotective in Parkinson disease cell models.
Meclizine-induced enhanced glycolysis is neuroprotective in Parkinson disease cell models.
复制标题
DOI：
10.1038/srep25344
复制
发表时间：
2016-05-05
影响因子：
4.6
通讯作者：
Schapira AH
中科院分区：
文献类型：
--
作者：
Hong CT;Chau KY;Schapira AH
美克洛嗪是一种耐受性良好的药物，通常用作治疗失衡的抗组胺药。最近，在缺血性中风和亨廷顿病模型中评估了美克洛嗪的神经保护特性。我们发现，美克洛嗪保护6-羟基多巴胺诱导的细胞凋亡和细胞死亡的SH-SY 5 Y细胞和大鼠原代皮层培养。美克洛嗪可增加6-磷酸果糖-2-激酶/果糖-2，6-二磷酸酶3（PFKFB 3）的水平，该酶可激活糖酵解的速率决定酶磷酸果糖激酶。因此，这种保护作用是由美克洛嗪增强糖酵解和增加线粒体超极化的能力介导的。美克洛嗪代表了一个值得进一步研究的候选药物，以重新确定其在帕金森病中具有神经保护作用的潜力。
Meclizine is a well-tolerated drug routinely used as an anti-histamine agent in the management of disequilibrium. Recently, meclizine has been assessed for its neuroprotective properties in ischemic stroke and Huntington disease models. We found that meclizine protected against 6-hydroxydopamine-induced apoptosis and cell death in both SH-SY5Y cells and rat primary cortical cultures. Meclizine increases the level of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), which activates phosphofructokinase, a rate-determining enzyme of glycolysis. This protection is therefore mediated by meclizine’s ability to enhance glycolysis and increase mitochondrial hyperpolarization. Meclizine represents an interesting candidate for further investigation to re-purpose for its potential to be neuroprotective in Parkinson disease.