Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases
Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases
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在模型和临床数据库中，增强糖酵解可减轻帕金森病的进展
DOI：
10.1172/jci129987
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发表时间：
2019-10-01
影响因子：
15.9
通讯作者：
Li, Lei
中科院分区：
文献类型：
--
作者：
Cai, Rong;Zhang, Yu;Li, Lei
帕金森病（PD）是一种常见的神经退行性疾病，缺乏预防进行性神经退行性疾病的治疗方法。能量代谢受损和ATP水平降低是帕金森病的共同特征。先前的研究表明，terazosin （TZ）增强磷酸甘油激酶1 （PGK1）的活性，从而刺激糖酵解并增加细胞ATP水平。因此，我们想知道PGK1活性的增强是否会改变PD的病程。在小鼠、大鼠、果蝇和诱导多能干细胞的毒素诱导和遗传PD模型中，TZ增加了脑ATP水平，减缓或阻止了神经元的损失。该药增加了多巴胺水平，部分恢复了运动功能。因为TZ是临床上的处方，我们也询问了2个不同的人类数据库。我们发现，在服用TZ和相关药物的个体中，疾病进展较慢，PD相关并发症减少，PD诊断频率降低。这些发现表明，增强PGK1活性和增加糖酵解可能减缓PD的神经退行性变。
Parkinson's disease (PD) is a common neurodegenerative disease that lacks therapies to prevent progressive neurodegeneration. Impaired energy metabolism and reduced ATP levels are common features of PD. Previous studies revealed that terazosin (TZ) enhances the activity of phosphoglycerate kinase 1 (PGK1), thereby stimulating glycolysis and increasing cellular ATP levels. Therefore, we asked whether enhancement of PGK1 activity would change the course of PD. In toxin-induced and genetic PD models in mice, rats, flies, and induced pluripotent stem cells, TZ increased brain ATP levels and slowed or prevented neuron loss. The drug increased dopamine levels and partially restored motor function. Because TZ is prescribed clinically, we also interrogated 2 distinct human databases. We found slower disease progression, decreased PD-related complications, and a reduced frequency of PD diagnoses in individuals taking TZ and related drugs. These findings suggest that enhancing PGK1 activity and increasing glycolysis may slow neurodegeneration in PD.