Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Al Ain, United Arab Emirates.
Traffic. 2023 Aug;24(8):312-333. doi: 10.1111/tra.12902. Epub 2023 May 15.
Endoplasmic reticulum-associated protein degradation (ERAD) is a stringent quality control mechanism through which misfolded, unassembled and some native proteins are targeted for degradation to maintain appropriate cellular and organelle homeostasis. Several in vitro and in vivo ERAD-related studies have provided mechanistic insights into ERAD pathway activation and its consequent events; however, a majority of these have investigated the effect of ERAD substrates and their consequent diseases affecting the degradation process. In this review, we present all reported human single-gene disorders caused by genetic variation in genes that encode ERAD components rather than their substrates. Additionally, after extensive literature survey, we present various genetically manipulated higher cellular and mammalian animal models that lack specific components involved in various stages of the ERAD pathway.
内质网相关蛋白降解（ERAD）是一种严格的质量控制机制，通过该机制，错误折叠、未组装和一些天然蛋白质被靶向降解，以维持适当的细胞和细胞器内稳态。一些体外和体内的 ERAD 相关研究为 ERAD 途径的激活及其后续事件提供了机制上的见解；然而，其中大多数研究都是在研究 ERAD 底物及其随后影响降解过程的疾病的影响。在这篇综述中，我们介绍了所有已报道的人类单基因疾病，这些疾病是由于编码 ERAD 成分的基因发生遗传变异而不是其底物引起的。此外，经过广泛的文献调查，我们介绍了各种经过基因改造的高等细胞和哺乳动物动物模型，这些模型缺乏 ERAD 途径各个阶段所涉及的特定成分。
