Adav Sunil S
School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.
Proteomes. 2025 Jun 5;13(2):24. doi: 10.3390/proteomes13020024.
Protein deamidation, a nonenzymatic post-translational modification that converts asparagine and glutamine residues into their acidic forms, such as aspartic acid, iso-aspartic acid, or glutamic acid, has emerged as a pivotal process affecting protein stability and function. Once considered a minor biochemical occurrence, deamidation is now recognized for its significant role in aging, age-associated diseases, disease progression, cancer, and therapeutic efficacy. This review explores the recent advances in understanding protein deamidation, its impact on cellular homeostasis, protein misfolding, and age-related and chronic diseases including neurodegeneration and cancer. The study also highlights the challenges posed by deamidation in biopharmaceuticals, where it compromises therapeutic stability and efficacy. Advancements in state-of-the-art analytical techniques and computational approaches for identifying deamidation sites and predicting deamidation-prone regions are discussed, along with deeper insights into how deamidation affects protein structure and function. Based on the current insights, this review underscores the dual role of deamidation as both a natural regulatory process and a contributor to pathological states, providing a roadmap for future research in aging biology, disease mechanisms, and therapeutics.
蛋白质脱酰胺作用是一种非酶促翻译后修饰，可将天冬酰胺和谷氨酰胺残基转化为其酸性形式，如天冬氨酸、异天冬氨酸或谷氨酸，已成为影响蛋白质稳定性和功能的关键过程。脱酰胺作用曾被视为一种次要的生化现象，如今因其在衰老、与年龄相关的疾病、疾病进展、癌症和治疗效果中所起的重要作用而受到认可。本综述探讨了在理解蛋白质脱酰胺作用、其对细胞稳态、蛋白质错误折叠以及包括神经退行性变和癌症在内的与年龄相关和慢性疾病的影响方面的最新进展。该研究还强调了脱酰胺作用给生物制药带来的挑战，因为它会损害治疗稳定性和疗效。文中讨论了用于识别脱酰胺位点和预测易发生脱酰胺区域的先进分析技术和计算方法的进展，以及对脱酰胺作用如何影响蛋白质结构和功能的更深入见解。基于当前的见解，本综述强调了脱酰胺作用作为一种自然调节过程和病理状态促成因素的双重作用，为衰老生物学、疾病机制和治疗学的未来研究提供了路线图。
