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

Abstract

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.

Challenges in Discovering Drugs That Target the Protein–Protein Interactions of Disordered Proteins

“…Protein kinases, such as GSK-3, Fyn, and DYRK1A, are central to neurodegenerative diseases because of their regulatory roles in different signal transduction cascades; multi-target inhibitors of such kinases prevented neurotoxin-induced cell death in in vitro PD models (for references see [98]). Analysis of disease-related genes and PPI networks may help in the development of potential drugs, as shown for AD [99].…”

Drug repositioning in non-small cell lung cancer (NSCLC) using gene co-expression and drug–gene interaction networks analysis

“…Drug repositioning is also referred to as drug repurposing, drug therapeutic, drug recycling, and drug reprofiling 13 , 14 . There are usually three kinds of methods for drug repurposing, including experimental biological methods, computational methods, and mixed methods 10 , 15 , 16 . Computational methods can be referred to as molecular docking, network mapping, signature matching, genetic association, and retrospective clinical analysis 13 , 17 , 18 .…”

“…Gene co-expression network analysis is one of the important network-based approaches in systems biology 11 , 31 , 32 . Different studies based on gene co-expression network analysis were done on different transcriptomic datasets.…”

Application of Protein-Protein interaction network analysis in order to identify Cervical cancer mRNA and miRNA biomarkers

“…In this regard, miRNA-mRNA interaction networks have been studied in different cancer studies. Negar and colleagues [21] introduced a miRNA-mRNA network-based biomarker for Alzheimer disease. Beside, Habib at al.…”