美国怀特黑德生物医学研究所Richard A. Young和Tong Ihn Lee共同合作，近期取得重要工作进展。他们研究提出，蛋白质迁移率降低是慢性疾病的致病机制之一。相关研究成果2024年11月27日在线发表于《细胞》杂志上。

据介绍，许多疾病的致病机制在分子水平上已被很好地理解，但也有与致病信号相关的常见综合征，如糖尿病和慢性炎症，人们对其的理解较为有限。

研究人员发现，致病性信号抑制了一系列蛋白质的流动性，这些蛋白质在已知的这些慢性疾病中失调的细胞功能中起着至关重要的作用。

蛋白质迁移率降低（研究人员称之为Proteolethargy）与受影响蛋白质中的半胱氨酸残基，和过量活性氧的信号相关增加有关。不同的致病刺激，包括高血糖、血脂异常和炎症，会产生类似的蛋白质迁移率降低表型。

总之，这一研究表明蛋白质能量是一种被忽视的细胞机制，可能解释了各种慢性疾病的各种致病特征。

附：英文原文

Title: Proteolethargy is a pathogenic mechanism in chronic disease

Author: Alessandra Dall’Agnese, Ming M. Zheng, Shannon Moreno, Jesse M. Platt, An T. Hoang, Deepti Kannan, Giuseppe Dall’Agnese, Kalon J. Overholt, Ido Sagi, Nancy M. Hannett, Hailey Erb, Olivia Corradin, Arup K. Chakraborty, Tong Ihn Lee, Richard A. Young

Issue&Volume:

Abstract: The pathogenic mechanisms of many diseases are well understood at the molecular level, but there are prevalent syndromes associated with pathogenic signaling, such as diabetes and chronic inflammation, where our understanding is more limited. Here, we report that pathogenic signaling suppresses the mobility of a spectrum of proteins that play essential roles in cellular functions known to be dysregulated in these chronic diseases. The reduced protein mobility, which we call proteolethargy, was linked to cysteine residues in the affected proteins and signaling-related increases in excess reactive oxygen species. Diverse pathogenic stimuli, including hyperglycemia, dyslipidemia, and inflammation, produce similar reduced protein mobility phenotypes. We propose that proteolethargy is an overlooked cellular mechanism that may account for various pathogenic features of diverse chronic diseases.

DOI: 10.1016/j.cell.2024.10.051

Source: https://www.cell.com/cell/abstract/S0092-8674(24)01274-1