Yang Zhiwei, Zhang Zichen, Zhao Yizhen, Ye Qiushi, Li Xuhua, Meng Lingjie, Long Jiangang, Zhang Shengli, Zhang Lei
MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, School of Physics, Xi'an Jiaotong University, Xi'an, China.
School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, China.
Front Pharmacol. 2022 Jun 20;13:935898. doi: 10.3389/fphar.2022.935898. eCollection 2022.
The inter-organelle interactions, including the cytomembrane, endoplasmic reticulum, mitochondrion, lysosome, dictyosome, and nucleus, play the important roles in maintaining the normal function and homeostasis of cells. Organelle dysfunction can lead to a range of diseases (e.g., Alzheimer's disease (AD), Parkinson's disease (PD), and cancer), and provide a new perspective for drug discovery. With the development of imaging techniques and functional fluorescent probes, a variety of algorithms and strategies have been developed for the ever-improving estimation of subcellular structures, organelle interaction, and organelle-related drug discovery with accounting for the dynamic structures of organelles, such as the nanoscopy technology and molecular dynamics (MD) simulations. Accordingly, this work summarizes a series of state-of-the-art examples of the recent progress in this rapidly changing field and uncovering the drug screening based on the structures and interactions of organelles. Finally, we propose the future outlook for exciting applications of organelle-related drug discovery, with the cooperation of nanoscopy and MD simulations.
包括细胞膜、内质网、线粒体、溶酶体、高尔基体和细胞核在内的细胞器间相互作用，在维持细胞的正常功能和体内平衡中发挥着重要作用。细胞器功能障碍可导致一系列疾病（如阿尔茨海默病（AD）、帕金森病（PD）和癌症），并为药物发现提供了新的视角。随着成像技术和功能性荧光探针的发展，已经开发出各种算法和策略，用于在考虑细胞器动态结构的情况下，不断改进对亚细胞结构、细胞器相互作用以及细胞器相关药物发现的评估，如纳米显微镜技术和分子动力学（MD）模拟。因此，这项工作总结了这个快速变化领域近期进展的一系列最新实例，并揭示了基于细胞器结构和相互作用的药物筛选。最后，我们提出了在纳米显微镜和MD模拟的合作下，细胞器相关药物发现令人兴奋的应用前景。
