[关键词]
[摘要]
应激颗粒(SGs)是细胞在各种应激条件下,通过液-液相分离(LLPS)在细胞质中形成的无膜核糖核蛋白凝聚体。SGs的组装主要依赖于整合应激反应核心的真核翻译起始因子2α磷酸化通路,也可独立于此通路,其动态过程由RNA结合蛋白特有的低复杂度结构域驱动; 而细胞内的蛋白质质量控制系统则介导其解聚。尽管SGs在神经退行性疾病中的致病作用已被广泛报道,但其在眼科疾病——特别是青光眼、年龄相关性黄斑变性和糖尿病视网膜病变中的功能仍处于探索阶段。文章系统梳理了近年来关于SGs在上述主要致盲性眼病中的研究进展,重点阐述了关键RNA结合蛋白(RBPs)如G3BP1/2、TIA-1、TDP-43、FUS在眼组织中的表达与功能变化,以及LLPS介导的相关信号通路(如PERK-eIF2α、Nrf2、mTOR、NLRP3炎症小体)的调控机制。文章旨在为理解致盲性眼科疾病的分子机制提供新的视角,并为开发靶向SGs动力学的新型干预策略提供理论依据。
[Key word]
[Abstract]
Stress granules(SGs)are membraneless ribonucleoprotein condensates formed in the cytoplasm via liquid-liquid phase separation(LLPS)under various stress conditions. Their assembly mainly depends on phosphorylation of eukaryotic translation initiation factor 2α(eIF2α), which is central to the integrated stress response, but can also occur independently of this pathway. Their dynamics are driven by the low-complexity domains characteristic of RNA-binding proteins(RBPs), while the intracellular protein quality control system mediates their disassembly.Although the role of SGs in neurodegenerative diseases has been extensively reported, but their functions in ocular diseases—particularly glaucoma, age-related macular degeneration(ARMD), and diabetic retinopathy(DR)—are still in the exploratory stage. This review summarizes recent research progress on SGs in these major blinding eye diseases, focusing on the expression and functional changes of key RBPs(such as G3BP1/2, TIA-1, TDP-43, and FUS)and the regulatory mechanisms of LLPS-related signaling pathways, including PERK-eIF2α, Nrf2, mTOR, and the NLRP3 inflammasome. This review aims to provide new insights into the molecular mechanisms of blinding ocular diseases and to offer a theoretical basis for the development of therapeutic strategies targeting SG dynamics.
[中图分类号]
[基金项目]
深圳市医学研究专项项目(No.A2303042); 爱尔眼科医院集团科研基金项目(No.AGF2301D29); 深圳爱尔眼科医院科研项目(No.SZAE2023A01)