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Discovering biomarkers and pathways shared by Alzheimer's Disease and ischemic stroke to identify novel therapeutic targets

Abstract

Background and objectives: Alzheimer's disease (AD) is a progressive neurodegenerative disease that results in severe dementia. Having ischemic strokes (IS) is one of the risk factors of the AD, but the molecular mechanisms that underlie IS and AD are not well understood. We thus aimed to identify common molecular biomarkers and pathways in IS and AD that can help predict the progression of these diseases and provide clues to important pathological mechanisms. Materials and Methods: We have analyzed the microarray gene expression datasets of IS and AD. To obtain robust results, combinatorial statistical methods were used to analyze the datasets and 26 transcripts (22 unique genes) were identified that were abnormally expressed in both IS and AD. Results: Gene Ontology (GO) and KEGG pathway analyses indicated that these 26 common dysregulated genes identified several altered molecular pathways: Alcoholism, MAPK signaling, glycine metabolism, serine metabolism, and threonine metabolism. Further protein-protein interactions (PPI) analysis revealed pathway hub proteins PDE9A, GNAO1, DUSP16, NTRK2, PGAM2, MAG, and TXLNA. Transcriptional and post-transcriptional components were then identified, and significant transcription factors (SPIB, SMAD3, and SOX2) found. Conclusions: Protein-drug interaction analysis revealed PDE9A has interaction with drugs caffeine, gamma-glutamyl glycine, and 3-isobutyl-1-methyl-7H-xanthine. Thus, we identified novel putative links between pathological processes in IS and AD at transcripts levels, and identified possible mechanistic and gene expression links between IS and AD.

Type Journal
ISBN 1648-9144 (Electronic) 1010-660X (Linking)
Authors Rahman, M. R.; Islam, T.; Shahjaman, M.; Zaman, T.; Faruquee, H. M.; Jamal, Mahm; Huq, F.; Quinn, J. M. W.; Moni, M. A.
Responsible Garvan Author Dr Mohammad Ali Moni
Publisher Name MEDICINA CLINICA
Published Date 2019-05-22
Published Volume 55
Published Issue 5
Published Pages E191
Status Always Electronic
DOI 10.3390/medicina55050191
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/31121943