Raju Chithra, Sankaranarayanan Kavitha
Ion Channel Biology Laboratory, AU-KBC Research Centre, Madras Institute of Technology Campus, Anna University, Chrompet, Chennai 600 044, Tamil Nadu, India.
Ion Channel Biology Laboratory, AU-KBC Research Centre, Madras Institute of Technology Campus, Anna University, Chrompet, Chennai 600 044, Tamil Nadu, India.
Biochim Biophys Acta Mol Basis Dis. 2025 Mar;1871(3):167659. doi: 10.1016/j.bbadis.2025.167659. Epub 2025 Jan 7.
Metabolic dysfunction-associated steatotic liver disease [MASLD] is a pervasive multifactorial health burden. Post-translational modifications [PTMs] of amino acid residues in protein domains demonstrate pivotal roles for imparting dynamic alterations in the cellular micro milieu. The crux of identifying novel druggable targets relies on comprehensively studying the etiology of metabolic disorders. This review article presents how different chemical moieties of various PTMs like phosphorylation, methylation, ubiquitination, glutathionylation, neddylation, acetylation, SUMOylation, lactylation, crotonylation, hydroxylation, glycosylation, citrullination, S-sulfhydration and succinylation presents the cause-effect contribution towards the MASLD spectra. Additionally, the therapeutic prospects in the management of liver steatosis and hepatic fibrosis via targeting PTMs and regulatory enzymes are also encapsulated. This review seeks to understand the function of protein modifications in progression and promote the markers discovery of diagnostic, prognostic and drug targets towards MASLD management which could also halt the progression of a catalogue of related diseases.
代谢功能障碍相关脂肪性肝病[MASLD]是一种普遍存在的多因素健康负担。蛋白质结构域中氨基酸残基的翻译后修饰[PTMs]在赋予细胞微环境动态变化方面发挥着关键作用。识别新型可成药靶点的关键在于全面研究代谢紊乱的病因。这篇综述文章介绍了各种PTMs的不同化学基团,如磷酸化、甲基化、泛素化、谷胱甘肽化、NEDD化、乙酰化、SUMO化、乳酸化、巴豆酰化、羟基化、糖基化、瓜氨酸化、S-巯基化和琥珀酰化,如何对MASLD谱产生因果影响。此外,还总结了通过靶向PTMs和调节酶来管理肝脂肪变性和肝纤维化的治疗前景。这篇综述旨在了解蛋白质修饰在疾病进展中的作用,并促进针对MASLD管理的诊断、预后和药物靶点的标志物发现,这也可能阻止一系列相关疾病的进展。