脑胶质瘤中异柠檬酸脱氢酶突变的研究进展

发布时间：2018-08-23 09:14

【摘要】：异柠檬酸脱氢酶(isocitrate dehvdrogenase,IDH)是三羧酸循环的关键酶,催化异柠檬酸氧化脱羧生成α-酮戌二酸(α-ketoglutaric acid,α-KG),同时利用烟酰胺腺嘌呤二核苷酸(nicotinamide adeninedinudeotide,NAD~+)/烟酰胺腺嘌呤二核苷磷酸(nicotinamide adenine dinucleotide phosphate,NADP~+)作为辅助因子生成还原型NADH/NADPH。超过75%的低级别胶质瘤(WHO分级为Ⅱ和Ⅲ级)和90%的继发性成胶质细胞瘤中存在IDH基因突变,且主要突变位点为R132H(132位精氨酸突变为组氨酸)。IDH基因突变改变了胶质瘤的表观遗传学特征,使胶质瘤代谢重编程,破坏胶质瘤氧化还原稳态。以突变的IDH基因为治疗靶点能抑制胶质瘤的进展,可用于新的抗肿瘤药物的研发。
[Abstract]:Isocitrate dehydrogenase (isocitrate dehvdrogenase idh) is a key enzyme in the tricarboxylic acid cycle. 伪 -ketoglutaric acid (伪 -KG) was synthesized by catalytic oxidation of isocitric acid to 伪 -ketoglutaric acid (伪 -KG). At the same time, nicotinamide adenine dinucleotide (NAD ~) / nicotinamide adenine dinucleotide phosphate (nicotinamide adenine dinucleotide) was used as an auxiliary factor to produce reduced NADH / NADPH. More than 75% of low-grade gliomas (WHO grade 鈪，

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