蛋白降解靶向嵌合体靶向治疗炎症免疫性疾病研究进展OA

Inflammatory and immune diseases are characterized by complex pathogenesis and protracted disease courses.Current treatment approaches are often limited by suboptimal efficacy,insufficient targeting specificity,and poor tolerability.Pro-teolysis-targeting chimeras(PROTACs)specifically degrade target proteins via mediating the ubiquitin-proteasome system,offer-ing a novel strategy to overcome the limitations of traditional therapies.This review systematically delineates the research advances of PROTAC technology in inflammatory and immune diseases,with particular emphasis on elucidating its targeted intervention mechanisms against pivotal signaling cascades and regulatory nodes.These encompass the JAK-STAT axis,BTK,IRAK,RIPK,as well as epigenetic modulators and oxidative stress sensors,notably HDACs and Keap1.Furthermore,this paper discusses the challenges encountered in the clinical translation process,optimization strategies,and future directions for development.