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

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作  者:舒凯[1] Shu Kai(Department of Neurosurgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区:[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

出  处:《中华实验外科杂志》2024年第9期1937-1940,共4页Chinese Journal of Experimental Surgery

基  金:华中科技大学同济医学院附属医院科研项目(2021049、2023081)。

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.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 

分 类 号:R739.4[医药卫生—肿瘤]

 

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