Liu Yukun, Zhang Haolin, Li Xianghua, He Tianlong, Zhang Wenting, Ji Cuicui, Wang Juan
College of Chemistry and Life Science, Beijing University of Technology, 100 Pingleyuan, Chaoyang District, Beijing, 100124, China.
Mol Biol Rep. 2025 Feb 15;52(1):236. doi: 10.1007/s11033-025-10316-6.
Unconventional protein secretion (UcPS) encompasses diverse non-canonical cellular export mechanisms that operate independently of the classical secretory pathway, representing a crucial cellular response to various physiological and pathological conditions. This comprehensive review synthesizes current understanding of UcPS mechanisms, particularly focusing on their roles in disease pathogenesis and progression. Recent advances in proteomics and cellular biology have revealed that UcPS facilitates the secretion of various biomedically significant proteins, including inflammatory mediators, growth factors, and disease-associated proteins, through multiple pathways such as membrane translocation, secretory lysosomes, and membrane-bound organelles. Notably, dysregulation of UcPS mechanisms has been implicated in various pathological conditions, including chronic inflammation, neurodegenerative disorders, and malignant transformation. We critically evaluate the molecular machinery governing UcPS, its regulation under cellular stress, and its contribution to disease mechanisms. Furthermore, we examine emerging therapeutic strategies targeting UcPS pathways, highlighting both opportunities and challenges in developing novel interventional approaches.
非传统蛋白质分泌（UcPS）涵盖了多种独立于经典分泌途径的非经典细胞输出机制，是细胞对各种生理和病理状况的关键反应。这篇综述综合了目前对UcPS机制的理解，尤其关注其在疾病发病机制和进展中的作用。蛋白质组学和细胞生物学的最新进展表明，UcPS通过膜易位、分泌性溶酶体和膜结合细胞器等多种途径促进各种具有重要生物医学意义的蛋白质的分泌，包括炎症介质、生长因子和疾病相关蛋白。值得注意的是，UcPS机制的失调与各种病理状况有关，包括慢性炎症、神经退行性疾病和恶性转化。我们批判性地评估了调控UcPS的分子机制、其在细胞应激下的调节及其对疾病机制的贡献。此外，我们研究了针对UcPS途径的新兴治疗策略，强调了开发新型干预方法的机遇和挑战。
