Exploring the common pathogenesis of Alzheimer’s disease and type 2 diabetes mellitus via microarray data analysis

Ye, Xianwen; Liu, Mengnan; Wang, Xuan; Cheng, Shui-qing; Li, Chun-shuai; Bai, Yuying; Yang, Linlin; Wang, Xu-xing; Wen, Jia; Xu, Wei; Zhang, Shuyan; Xu, Xin-fang; Li, Xiang-Ri

doi:10.3389/fnagi.2023.1071391

Cited by 3 publications

(2 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… Lee and Lee (2021) constructed a co-expression network to identify COPS4, PSMA6, GTF2B, GTF2F2, and SSB as dysregulated transcription common factors between AD and DM. Ye et al (2023) identified 10 shared hub genes between AD and T2D. Afzal et al (2023) uncovered the mutual genomics motifs between AD and T2D via non-negative matrix factorization, and screened of six shared genes.…”

Section: Identification Of Shared Candidate Biomarkers Between Ad And...mentioning

confidence: 99%

A review and analysis of key biomarkers in Alzheimer’s disease

Zhang,

Liu,

Zhang

et al. 2024

Front. Neurosci.

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that affects over 50 million elderly individuals worldwide. Although the pathogenesis of AD is not fully understood, based on current research, researchers are able to identify potential biomarker genes and proteins that may serve as effective targets against AD. This article aims to present a comprehensive overview of recent advances in AD biomarker identification, with highlights on the use of various algorithms, the exploration of relevant biological processes, and the investigation of shared biomarkers with co-occurring diseases. Additionally, this article includes a statistical analysis of key genes reported in the research literature, and identifies the intersection with AD-related gene sets from databases such as AlzGen, GeneCard, and DisGeNet. For these gene sets, besides enrichment analysis, protein–protein interaction (PPI) networks utilized to identify central genes among the overlapping genes. Enrichment analysis, protein interaction network analysis, and tissue-specific connectedness analysis based on GTEx database performed on multiple groups of overlapping genes. Our work has laid the foundation for a better understanding of the molecular mechanisms of AD and more accurate identification of key AD markers.

show abstract

Section: Identification Of Shared Candidate Biomarkers Between Ad And...mentioning

confidence: 99%

A review and analysis of key biomarkers in Alzheimer’s disease

Zhang,

Liu,

Zhang

et al. 2024

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Previous studies uncovered genes and signatures crosstalk linked these two diseases [45][46][47][48]. Herein, DEGs between AD and control included 381 downregulated genes and 357 upregulated genes in the dataset GSE122063 (▶ Fig.…”

Section: Cross-analysis Of the Molecular Links Between Type 2 Diabete...mentioning

confidence: 99%

Beneficial Effects of Echinacoside on Cognitive Impairment and Diabetes in Type 2 Diabetic db/db Mice

Qin,

Yan,

Yang

et al. 2024

Exp Clin Endocrinol Diabetes

View full text Add to dashboard Cite

Cognitive dysfunction is an important comorbidity of diabetes. Insulin resistance may play a critical role in diabetes-related cognitive impairment. Echinacoside(ECH), a natural phenylethanoid glycoside, is the active component of anti-diabetes prescriptions in traditional Chinese medicine. Its effect on modulating insulin resistance has been confirmed but modulating neurodegenerative disease still remains to be clarified. Db/db mice, a spontaneous Type 2 diabetes （T2D）mode, were intragastrically administered various doses of ECH or an equivalent volume of saline. Weight, blood glucose, and insulin resistance index were measured. Morris water maze was used to observe the compound effects on cognition. Hippocampal lesions were observed by histochemical analysis. In db/db mice, ECH alleviates diabetes symptoms, memory loss, and hippocampal neuronal damage.Following the step, we found CD44 and phosphorylated tau expression upregulated in diabetic mice. We also found the insulin receptor substrate-1 (IRS1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway dysregulated in diabetic mice. All these changes could be reversed by ECH. Our study provides theoretical support and experimental evidence for the future application of ECH in diabetic cognition dysfunction treatment, promoting the development of traditional medicines.

show abstract

Network analysis-guided drug repurposing strategies targeting LPAR receptor in the interplay of COVID, Alzheimer’s, and diabetes

Malar,

Verma,

Prasanth

et al. 2024

Sci Rep

View full text Add to dashboard Cite

The COVID-19 pandemic caused by the SARS-CoV-2 virus has greatly affected global health. Emerging evidence suggests a complex interplay between Alzheimer’s disease (AD), diabetes (DM), and COVID-19. Given COVID-19’s involvement in the increased risk of other diseases, there is an urgent need to identify novel targets and drugs to combat these interconnected health challenges. Lysophosphatidic acid receptors (LPARs), belonging to the G protein-coupled receptor family, have been implicated in various pathological conditions, including inflammation. In this regard, the study aimed to investigate the involvement of LPARs (specifically LPAR1, 3, 6) in the tri-directional relationship between AD, DM, and COVID-19 through network analysis, as well as explore the therapeutic potential of selected anti-AD, anti-DM drugs as LPAR, SPIKE antagonists. We used the Coremine Medical database to identify genes related to DM, AD, and COVID-19. Furthermore, STRING analysis was used to identify the interacting partners of LPAR1, LPAR3, and LPAR6. Additionally, a literature search revealed 78 drugs on the market or in clinical studies that were used for treating either AD or DM. We carried out docking analysis of these drugs against the LPAR1, LPAR3, and LPAR6. Furthermore, we modeled the LPAR1, LPAR3, and LPAR6 in a complex with the COVID-19 spike protein and performed a docking study of selected drugs with the LPAR-Spike complex. The analysis revealed 177 common genes implicated in AD, DM, and COVID-19. Protein–protein docking analysis demonstrated that LPAR (1,3 & 6) efficiently binds with the viral SPIKE protein, suggesting them as targets for viral infection. Furthermore, docking analysis of the anti-AD and anti-DM drugs against LPARs, SPIKE protein, and the LPARs-SPIKE complex revealed promising candidates, including lupron, neflamapimod, and nilotinib, stating the importance of drug repurposing in the drug discovery process. These drugs exhibited the ability to bind and inhibit the LPAR receptor activity and the SPIKE protein and interfere with LPAR-SPIKE protein interaction. Through a combined network and targeted-based therapeutic intervention approach, this study has identified several drugs that could be repurposed for treating COVID-19 due to their expected interference with LPAR(1, 3, and 6) and spike protein complexes. In addition, it can also be hypothesized that the co-administration of these identified drugs during COVID-19 infection may not only help mitigate the impact of the virus but also potentially contribute to the prevention or management of post-COVID complications related to AD and DM.

show abstract

Exploring the common pathogenesis of Alzheimer’s disease and type 2 diabetes mellitus via microarray data analysis

Cited by 3 publications

References 52 publications

A review and analysis of key biomarkers in Alzheimer’s disease

A review and analysis of key biomarkers in Alzheimer’s disease

Beneficial Effects of Echinacoside on Cognitive Impairment and Diabetes in Type 2 Diabetic db/db Mice

Network analysis-guided drug repurposing strategies targeting LPAR receptor in the interplay of COVID, Alzheimer’s, and diabetes

Contact Info

Product

Resources

About