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Liu D, Dai SX, He K, et al. Identification of hub ubiquitin ligase genes affecting Alzheimer's disease by analyzing transcriptome data from multiple brain regions. Sci Prog. 2021;104(1):368504211001146doi: 10.1177/00368504211001146.
Liu, D., Dai, S. X., He, K., Li, G. H., Liu, J., Liu, L. G., Huang, J. F., Xu, L., & Li, W. X. (2021). Identification of hub ubiquitin ligase genes affecting Alzheimer's disease by analyzing transcriptome data from multiple brain regions. Science progress, 104(1), 368504211001146. https://doi.org/10.1177/00368504211001146
Liu, Dahai, et al. "Identification of hub ubiquitin ligase genes affecting Alzheimer's disease by analyzing transcriptome data from multiple brain regions." Science progress vol. 104,1 (2021): 368504211001146. doi: https://doi.org/10.1177/00368504211001146
Liu D, Dai SX, He K, Li GH, Liu J, Liu LG, Huang JF, Xu L, Li WX. Identification of hub ubiquitin ligase genes affecting Alzheimer's disease by analyzing transcriptome data from multiple brain regions. Sci Prog. 2021 Jan-Mar;104(1):368504211001146. doi: 10.1177/00368504211001146. PMID: 33754896.
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Sci Prog. 2021 Jan-Mar;104(1):368504211001146. doi: 10.1177/00368504211001146.

Identification of hub ubiquitin ligase genes affecting Alzheimer's disease by analyzing transcriptome data from multiple brain regions.

Science progress

Dahai Liu, Shao-Xing Dai, Kan He, Gong-Hua Li, Justin Liu, Leyna G Liu, Jing-Fei Huang, Lin Xu, Wen-Xing Li

Affiliations

  1. Foshan Stomatology Hospital, School of Medicine, Foshan University, Foshan, Guangdong, China.
  2. Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China.
  3. School of Life Sciences, Auhui University, Hefei, Anhui, China.
  4. State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
  5. Department of Statistics, University of California, Riverside, CA, USA.
  6. Portola High School, Irvine, CA, USA.
  7. Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China.
  8. Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China.
  9. Centre for Excellence in Brain Science and Intelligent Technology, Chinese Academy of Sciences, Shanghai, China.

PMID: 33754896 DOI: 10.1177/00368504211001146

Abstract

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.

Keywords: Alzheimer’s disease; brain region; gene expression; ubiquitin ligases; ubiquitin-proteasome system

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