Chen Rong, Tang Xiaohua, Wang Ying, Wang Bo, Mao Fei
Key Laboratory of Medical Science and Laboratory Medicine of Jiangsu Province, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
Department of Laboratory Medicine, the Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China.
Front Immunol. 2025 Sep 1;16:1652741. doi: 10.3389/fimmu.2025.1652741. eCollection 2025.
Protein palmitoylation is a reversible lipid modification in which palmitoyl esters are covalently attached to cysteine residues of proteins. It controls various cellular physiological processes and alters protein stability, conformation, localization, membrane binding, and interaction with other effector proteins. Palmitoylation is catalyzed by a group of zinc finger DHHC-containing proteins (ZDHHCs), while the acyl-protein thioesterase family mediates depalmitoylation. Emerging evidence suggests that palmitoylation is critical for inflammatory signaling pathways, where palmitoylation is particularly important in the membrane localization of inflammation-associated proteins. Notably, dysregulation of palmitoylation has been associated with a variety of inflammatory diseases. Here, we provide an overview of the regulatory mechanisms of palmitoylation, explore the emerging role of palmitoylation in inflammatory signaling pathways, and examine the link between dysregulated palmitoylation and the pathogenesis of inflammatory diseases, including inflammatory bowel disease, autoimmune diseases, metabolic dysfunction-associated steatohepatitis, sepsis, Alzheimer's disease, Parkinson's disease, and diabetes. Finally, we discuss some of the challenges and opportunities facing the field. Targeting palmitoylation or its associated enzymes serves as a novel therapeutic approach for the treatment of inflammatory diseases.
蛋白质棕榈酰化是一种可逆的脂质修饰，其中棕榈酰酯共价连接到蛋白质的半胱氨酸残基上。它控制着各种细胞生理过程，并改变蛋白质的稳定性、构象、定位、膜结合以及与其他效应蛋白的相互作用。棕榈酰化由一组含锌指结构域的DHHC蛋白（ZDHHCs）催化，而酰基蛋白硫酯酶家族介导去棕榈酰化。新出现的证据表明，棕榈酰化对炎症信号通路至关重要，在炎症相关蛋白的膜定位中，棕榈酰化尤为重要。值得注意的是，棕榈酰化失调与多种炎症性疾病有关。在此，我们概述了棕榈酰化的调控机制，探讨了棕榈酰化在炎症信号通路中的新作用，并研究了棕榈酰化失调与炎症性疾病发病机制之间的联系，包括炎症性肠病、自身免疫性疾病、代谢功能障碍相关脂肪性肝炎、败血症、阿尔茨海默病、帕金森病和糖尿病。最后，我们讨论了该领域面临的一些挑战和机遇。靶向棕榈酰化或其相关酶是治疗炎症性疾病的一种新的治疗方法。
