Title:Viral Induced Oxidative and Inflammatory Response in Alzheimer’s Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach
Volume: 17
Issue: 4
Author(s): Puneet Talwar, Renu Gupta, Suman Kushwaha, Rachna Agarwal, Luciano Saso, Shrikant Kukreti and Ritushree Kukreti*
Affiliation:
- Genomics and Molecular Medicine Unit, Institute of Genomics and Integrative Biology (IGIB), Council of Scientific and Industrial Research (CSIR), Delhi,India
Keywords:
Alzheimer's disease, neurodegenerative disease, virus infection, genes, drug, protein-protein interaction, systematic
review.
Abstract: Alzheimer’s disease (AD) is genetically complex with multifactorial etiology. Here, we
aim to identify the potential viral pathogens leading to aberrant inflammatory and oxidative stress
response in AD along with potential drug candidates using systems biology approach. We retrieved
protein interactions of amyloid precursor protein (APP) and tau protein (MAPT) from NCBI and
genes for oxidative stress from NetAge, for inflammation from NetAge and InnateDB databases.
Genes implicated in aging were retrieved from GenAge database and two GEO expression datasets.
These genes were individually used to create protein-protein interaction network using STRING
database (score≥0.7). The interactions of candidate genes with known viruses were mapped using
virhostnet v2.0 database. Drug molecules targeting candidate genes were retrieved using the Drug-
Gene Interaction Database (DGIdb). Data mining resulted in 2095 APP, 116 MAPT, 214 oxidative
stress, 1269 inflammatory genes. After STRING PPIN analysis, 404 APP, 109 MAPT, 204
oxidative stress and 1014 inflammation related high confidence proteins were identified. The
overlap among all datasets yielded eight common markers (AKT1, GSK3B, APP, APOE, EGFR,
PIN1, CASP8 and SNCA). These genes showed association with hepatitis C virus (HCV), Epstein–
Barr virus (EBV), human herpes virus 8 and Human papillomavirus (HPV). Further, screening of
drugs targeting candidate genes, and possessing anti-inflammatory property, antiviral activity along
with a suggested role in AD pathophysiology yielded 12 potential drug candidates. Our study
demonstrated the role of viral etiology in AD pathogenesis by elucidating interaction of oxidative
stress and inflammation causing candidate genes with common viruses along with the identification
of potential AD drug candidates.