Direct inhibition of Keap1-Nrf2 Protein-Protein interaction as a potential therapeutic strategy for Alzheimer's disease

2020 ◽  
Vol 103 ◽  
pp. 104172 ◽  
Author(s):  
Yi Sun ◽  
Jiaxuan Huang ◽  
Yufei Chen ◽  
Hao Shang ◽  
Wannian Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interaction ◽  
Therapeutic Strategy ◽  
Direct Inhibition ◽  
Protein Protein Interaction ◽  
Nrf2 Protein

Putative Factors Interfering Cell Cycle Re-Entry in Alzheimer’s Disease: An Omics Study with Differential Expression Meta-Analytics and Co-Expression Profiling

2021 ◽  
pp. 1-26
Author(s):  
Sze Chung Yuen ◽  
Simon Ming-Yuen Lee ◽  
Siu-wai Leung
Keyword(s):  
Alzheimer’S Disease ◽  
Cell Cycle ◽  
Alzheimer's Disease ◽  
Expression Analysis ◽  
Protein Interaction ◽  
Meta Analysis ◽  
Differentially Expressed ◽  
Tau Proteins ◽  
Related Factors ◽  
Protein Protein Interaction

Background: Neuronal cell cycle re-entry (CCR) is a mechanism, along with amyloid-β (Aβ) oligomers and hyperphosphorylated tau proteins, contributing to toxicity in Alzheimer’s disease (AD). Objective: This study aimed to examine the putative factors in CCR based on evidence corroboration by combining meta-analysis and co-expression analysis of omic data. Methods: The differentially expressed genes (DEGs) and CCR-related modules were obtained through the differential analysis and co-expression of transcriptomic data, respectively. Differentially expressed microRNAs (DEmiRNAs) were extracted from the differential miRNA expression studies. The dysregulations of DEGs and DEmiRNAs as binary outcomes were independently analyzed by meta-analysis based on a random-effects model. The CCR-related modules were mapped to human protein-protein interaction databases to construct a network. The importance score of each node within the network was determined by the PageRank algorithm, and nodes that fit the pre-defined criteria were treated as putative CCR-related factors. Results: The meta-analysis identified 18,261 DEGs and 36 DEmiRNAs, including genes in the ubiquitination proteasome system, mitochondrial homeostasis, and CCR, and miRNAs associated with AD pathologies. The co-expression analysis identified 156 CCR-related modules to construct a protein-protein interaction network. Five genes, UBC, ESR1, EGFR, CUL3, and KRAS, were selected as putative CCR-related factors. Their functions suggested that the combined effects of cellular dyshomeostasis and receptors mediating Aβ toxicity from impaired ubiquitination proteasome system are involved in CCR. Conclusion: This study identified five genes as putative factors and revealed the significance of cellular dyshomeostasis in the CCR of AD.

scholarly journals Identification of Key Genes Related with Alzheimer’s Disease Treatment Through Bioinformatics Analysis

2018 ◽  
Vol 9 (1) ◽  
pp. 78
Author(s):  
Liqun Wang ◽  
Hongjia Qian ◽  
Liqun Wang
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interaction ◽  
Expression Profiles ◽  
Amyloid Β ◽  
Interaction Network ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Tg2576 Mice

T0901317, a live X receptor agonist, can reduce amyloid β generation in vitro and in a mouse Alzheimer’s disease (AD) model. To investigate the global molecular effects of T0901317 in mouse hippocampus, we downloaded public GSE31624 generated from the hippocampus of wild-type mice, Tg2576 mice and T0901317-treated Tg2576 mice. Differentially-expressed genes (DEGs) were identified on LIMMA of R software. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment were analyzed through DAVID. Protein- protein interaction and hub genes were obtained based on STRING and Cytoscape. Nine downregulated and 68 upregulated DEGs in T0901317-treated Tg2576 were identified in comparison with untreated Tg2576 mice. Annotation analyses showed these DEGs correlated with transport (BP), membrane (CC) and binding (MF) terms and the dopaminergic synapse pathway. Protein-protein interaction network was built to find out some hub genes by maximal clique centrality. Discs large homolog 4 (Dlg4), the most outstanding gene, was associated with cognition improvement in aged AD mice. T0901317 may impact the development by regulating the Dlg4 expression. In conclusion, we investigated effects of T0901317 therapy on gene expression profiles in the hippocampus of Tg2576 mice and found Dlg4 may serve as putative therapeutics target for AD treatment.

O2-13-06: The protein-protein interaction network analysis of neurobiology of Alzheimer's disease: A blood-based mirna systematic revision study

2015 ◽  
Vol 11 (7S_Part_4) ◽  
pp. P206-P207
Author(s):  
Ana Paula Mendes Silva ◽  
Kenia Kelly Fiaux do Nascimento ◽  
Kelly Silva Pereira ◽  
Eduardo de Souza Nicolau ◽  
Lucélia SilvaS Barroso ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Network Analysis ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
Interaction Network ◽  
Systematic Revision ◽  
Protein Protein Interaction ◽  
Protein Protein Interaction Network

scholarly journals Drug Repurposing for Alzheimer’s Disease Based on Protein-Protein Interaction Network

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Negar Sadat Soleimani Zakeri ◽  
Saeid Pashazadeh ◽  
Habib MotieGhader
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Interaction ◽  
Target Genes ◽  
Neurodegenerative Disorder ◽  
Gentian Violet ◽  
New Drugs ◽  
Medical Studies ◽  
Protein Protein Interaction ◽  
Gene Complexes

Alzheimer’s disease (AD) is known as a critical neurodegenerative disorder. It worsens as symptoms concerning dementia grow severe over the years. Due to the globalization of Alzheimer’s disease, its prevention and treatment are vital. This study proposes a method to extract substantial gene complexes and then introduces potential drugs in Alzheimer’s disease. To this end, a protein-protein interaction (PPI) network was utilized to extract five meaningful gene complexes functionally interconnected. An enrichment analysis to introduce the most important biological processes and pathways was accomplished on the obtained genes. The next step is extracting the drugs related to AD and introducing some new drugs which may be helpful for this disease. Finally, a complete network including all the genes associated with each gene complex group and genes’ target drug was illustrated. For validating the proposed potential drugs, Connectivity Map (CMAP) analysis was accomplished to determine target genes that are up- or downregulated by proposed drugs. Medical studies and publications were analyzed thoroughly to introduce AD-related drugs. This analysis proves the accuracy of the proposed method in this study. Then, new drugs were introduced that can be experimentally examined as future work. Raloxifene and gentian violet are two new drugs, which have not been introduced as AD-related drugs in previous scientific and medical studies, recommended by the method of this study. Besides the primary goal, five bipartite networks representing the genes of each group and their target miRNAs were constructed to introduce target miRNAs.

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