Foshan Stomatology Hospital, School of Medicine, Foshan University, Foshan, Guangdong, China.
Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.
Sci Prog. 2021 Jan-Mar;104(1):368504211001146. doi: 10.1177/00368504211001146.
The ubiquitin-proteasome system (UPS) plays crucial roles in numerous cellular functions. Dysfunction of the UPS shows certain correlations with the pathological changes in Alzheimer's disease (AD). This study aimed to explore the different impairments of the UPS in multiple brain regions and identify hub ubiquitin ligase (E3) genes in AD. The brain transcriptome, blood transcriptome and proteome data of AD were downloaded from a public database. The UPS genes were collected from the Ubiquitin and Ubiquitin-like Conjugation Database. The hub E3 genes were defined as the differentially expressed E3 genes shared by more than three brain regions. E3Miner and UbiBrowser were used to predict the substrate of hub E3. This study shows varied impairment of the UPS in different brain regions in AD. Furthermore, we identify seven hub E3 genes (CUL1, CUL3, EIF3I, NSMCE1, PAFAH1B1, RNF175, and UCHL1) that are downregulated in more than three brain regions. Three of these genes (CUL1, EIF3I, and NSMCE1) showed consistent low expression in blood. Most of these genes have been reported to promote AD, whereas the impact of RNF175 on AD is not yet reported. Further analysis revealed a potential regulatory mechanism by which hub E3 and its substrate genes may affect transcription functions and then exacerbate AD. This study identified seven hub E3 genes and their substrate genes affect transcription functions and then exacerbate AD. These findings may be helpful for the development of diagnostic biomarkers and therapeutic targets for AD.
泛素-蛋白酶体系统（UPS）在许多细胞功能中起着至关重要的作用。UPS 的功能障碍与阿尔茨海默病（AD）的病理变化有一定的相关性。本研究旨在探索 UPS 在多个脑区的不同损伤，并确定 AD 中的枢纽泛素连接酶（E3）基因。从公共数据库中下载 AD 的大脑转录组、血液转录组和蛋白质组数据。从泛素和泛素样连接酶数据库中收集 UPS 基因。定义枢纽 E3 基因为在三个以上脑区共享的差异表达 E3 基因。使用 E3Miner 和 UbiBrowser 预测枢纽 E3 的底物。本研究表明，AD 中不同脑区 UPS 的损伤程度不同。此外，我们确定了七个枢纽 E3 基因（CUL1、CUL3、EIF3I、NSMCE1、PAFAH1B1、RNF175 和 UCHL1）在三个以上脑区下调。其中三个基因（CUL1、EIF3I 和 NSMCE1）在血液中均表现出一致的低表达。这些基因中有许多已被报道可促进 AD 的发生，而 RNF175 对 AD 的影响尚未报道。进一步的分析揭示了一种潜在的调节机制，通过该机制，枢纽 E3 及其底物基因可能会影响转录功能，从而加重 AD。本研究确定了七个枢纽 E3 基因及其底物基因影响转录功能，从而加重 AD。这些发现可能有助于开发 AD 的诊断生物标志物和治疗靶点。
