乳酸及乳酸化修饰-胶质瘤基础研究新热点和新挑战
Lactate and lactylation in gliomas:new insight and new challenges
舒凯1
作者信息
- 1. 华中科技大学同济医学院附属同济医院神经外科,武汉 430030
- 折叠
摘要
胶质瘤是中枢神经系统中最常见的恶性肿瘤,具有恶性程度极高、预后差等特点.近十余年来,胶质瘤基础研究的热潮不断兴起,有效的结论却乏善可陈.乳酸作为糖酵解的常规产物,不仅参与代谢,还在肿瘤微环境中发挥重要作用.乳酸化修饰是一种于2019年发现的蛋白翻译后修饰,影响胶质瘤的代谢重编程、免疫逃逸和微环境塑造.靶向乳酸及乳酸化的治疗,如抑制乳酸脱氢酶(LDHA)或组蛋白的乳酸化修饰,显示出显著改善胶质母细胞瘤(GBM)预后的潜力.目前相关研究主要集中于胶质瘤细胞的组蛋白乳酸化,非组蛋白和其他胶质瘤组分乳酸化修饰的研究仍需进一步深入探索,以期为治疗提供确切有效的靶点.
Abstract
Gliomas are the most common malignant tumors of the central nervous system,charac-terized by high malignancy and poor prognosis.Over the last decade,a great number of researches were ap-plied to the cellular mechanisms of gliomas.However,most of them have been proven to be impracticable.Lactate,a regular product of glycolysis,not only participates in metabolism but also plays a significant role in the regulation of tumor microenvironment.Furthermore,lactylation,a post-translational modification dis-covered in 2019,is widely involved in metabolic reprogramming,immune evasion,and microenvironment shaping in gliomas.Therapeutic strategies targeting lactate and lactylation,such as inhibiting lactate dehy-drogenase(LDHA)or lactylation of histone,have shown inspiring effect in improving the prognosis of glio-blastoma(GBM).However,current researches are primarily restricted in histone lactylation,while non-histone lactylation and lactylation in other glioma components require further investigation to identify new and practicable therapeutic targets.
关键词
胶质瘤/胶质母细胞瘤/代谢/乳酸/翻译后修饰Key words
Glioma/Glioblastoma/Metabolism/Lactic Acid/Post-Translational Modifica-tion引用本文复制引用
出版年
2024
NETL
NSTL
万方数据