论文部分内容阅读
3-磷酸甘油醛脱氢酶(GAPDH)是一种经典的糖酵解蛋白,除了行使糖酵解功能外,还参与多种细胞生理功能。研究显示,GAPDH酶蛋白与帕金森病(PD)相关蛋白如α-突触核蛋白等有相互作用,参与Lewy小体形成,介导多种因素诱导的神经元细胞凋亡。gapdh基因过表达、GAPDH酶蛋白异常聚集和核转位与PD的发生有关。GAPDH在应激条件下发生巯基亚硝基化,巯基亚硝基化的GAPDH(SNO-GAPDH)通过与Siah1结合发生核转位,介导凋亡级联反应。司来吉兰及其结构类似物通过与GAPDH酶蛋白结合,干扰凋亡信号通路,发挥神经保护作用。GOSPEL(GAPDH’s competitor of siah protein enhances life)是一种新发现的GAPDH酶蛋白神经毒性通路中的负调节蛋白,可能为PD治疗提供新的靶点。
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a classical glycolysis protein that, in addition to its function of glycolysis, is involved in a variety of cellular physiological functions. Studies have shown that GAPDH enzyme protein and Parkinson’s disease (PD) related proteins such as α-synuclein and other interactions, involved in the formation of Lewy bodies, mediated by a variety of factors-induced neuronal apoptosis. GapDh gene overexpression, abnormal GAPDH enzyme protein aggregation and nuclear translocation with the occurrence of PD. GAPDH undergoes sulfhydryl nitrosylation under stress conditions and sulfhydryl nitrosylated GAPDH (SNO-GAPDH) mediates apoptosis cascade by binding to Siah1 for nuclear translocation. Selegiline and its structural analogues exert neuroprotective effects by binding to GAPDH enzyme proteins and interfering with apoptotic signaling pathways. GOSPEL (GAPDH’s competitor of siah protein enhances life) is a newly discovered negative regulator of the GAPDH enzyme protein neurotoxicity pathway, which may provide a new target for PD therapy.