Zhan Chenxi, Zhao Xuye, Wei Yaoxin, Yang Renqiang, Yan Nianlong
Huankui College, Jiangxi Medical College, Nanchang University, Nanchang 330000, Jiangxi, China.
Queen Mary College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330031, China.
Cell Signal. 2025 Oct;134:111971. doi: 10.1016/j.cellsig.2025.111971. Epub 2025 Jun 30.
NGLY1, a cytoplasmic enzyme, removes N-glycans from misfolded glycoproteins during endoplasmic reticulum-associated degradation (ERAD), a critical protein quality control mechanism. ERAD coordinates with the ubiquitin-proteasome system (UPS), working synergistically to maintain cellular proteostasis and mitigate protein toxicity. Emerging evidence highlights the multifaceted roles of NGLY1 in proteostasis activity, autophagy, endoplasmic reticulum stress, and related areas, all of which are connected to numerous diseases, including neurodegenerative disorders and cancer, among others. To fully understand the function of NGLY1 in cellular homeostasis, this review comprehensively discusses recent research progress and the related molecular mechanisms of NGLY1 in cellular homeostasis and associated diseases, as well as the therapeutic approaches.
NGLY1是一种胞质酶，在内质网相关降解（ERAD）过程中从错误折叠的糖蛋白中去除N -聚糖，ERAD是一种关键的蛋白质质量控制机制。ERAD与泛素 - 蛋白酶体系统（UPS）协同作用，共同维持细胞蛋白质稳态并减轻蛋白质毒性。新出现的证据凸显了NGLY1在蛋白质稳态活性、自噬、内质网应激及相关领域的多方面作用，所有这些都与包括神经退行性疾病和癌症等多种疾病相关。为全面了解NGLY1在细胞稳态中的功能，本综述全面讨论了NGLY1在细胞稳态及相关疾病中的最新研究进展、相关分子机制以及治疗方法。
