Zhang Ligang, Deng Ruiting, Liu Lian, Du Hongli, Tang Dongsheng
Gene Editing Technology Center of Guangdong Province, School of Medicine, Foshan University, Foshan, China.
School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.
Front Mol Biosci. 2024 Nov 26;11:1477971. doi: 10.3389/fmolb.2024.1477971. eCollection 2024.
Cuproptosis is a new pattern of Cu-dependent cell death distinct from classic cell death pathways and characterized by aberrant lipoylated protein aggregation in TCA cycle, Fe-S cluster protein loss, HSP70 elevation, proteotoxic and oxidative stress aggravation. Previous studies on Cu homeostasis and Cu-induced cell death provide a great basis for the discovery of cuproptosis. It has gradually gathered enormous research interests and large progress has been achieved in revealing the metabolic pathways and key targets of cuproptosis, due to its role in mediating some genetic, neurodegenerative, cardiovascular and tumoral diseases. In terms of the key targets in cuproptosis metabolic pathways, they can be categorized into three types: oxidative stress, mitochondrial respiration, ubiquitin-proteasome system. And strategies for developing cuproptosis inducers and inhibitors involved in these targets have been continuously improved. Briefly, based on the essential cuproptosis targets and metabolic pathways, this paper classifies some relevant inducers and inhibitors including small molecule compounds, transcription factors and ncRNAs with the overview of principle, scientific and medical application, in order to provide reference for the cuproptosis study and target therapy in the future.
铜死亡是一种新的铜依赖性细胞死亡模式，不同于经典的细胞死亡途径，其特征是三羧酸循环中异常的脂酰化蛋白聚集、铁硫簇蛋白丢失、热休克蛋白70升高、蛋白毒性和氧化应激加剧。先前关于铜稳态和铜诱导细胞死亡的研究为铜死亡的发现提供了重要基础。由于其在介导某些遗传、神经退行性、心血管和肿瘤疾病中的作用，它逐渐引起了巨大的研究兴趣，并且在揭示铜死亡的代谢途径和关键靶点方面取得了很大进展。就铜死亡代谢途径中的关键靶点而言，它们可分为三种类型：氧化应激、线粒体呼吸、泛素-蛋白酶体系统。并且针对这些靶点开发铜死亡诱导剂和抑制剂的策略也在不断改进。简而言之，基于铜死亡的关键靶点和代谢途径，本文对一些相关的诱导剂和抑制剂进行了分类，包括小分子化合物、转录因子和非编码RNA，并概述了其作用原理、科学和医学应用，以便为未来的铜死亡研究和靶向治疗提供参考。
