Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic Targets
<i>Background and objectives</i>: 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...
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doaj-7bd3344286b64b469f23d11cc5e461972020-11-25T01:18:27ZengMDPI AGMedicina1010-660X2019-05-0155519110.3390/medicina55050191medicina55050191Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic TargetsMd. Rezanur Rahman0Tania Islam1Md. Shahjaman2Toyfiquz Zaman3Hossain Md. Faruquee4Mohammad Abu Hena Mostofa Jamal5Fazlul Huq6Julian M. W. Quinn7Mohammad Ali Moni8Department of Biochemistry and Biotechnology, School of Biomedical Science, Khwaja Yunus Ali University, Sirajgonj 6751, BangladeshDepartment of Biotechnology and Genetic Engineering, Islamic University, Kushtia 7003, BangladeshDepartment of Statistics, Begum Rokeya University, Rangpur 5400, Bangladesh, <email>shahjaman_brur@yahoo.com</email>Department of Biochemistry and Biotechnology, School of Biomedical Science, Khwaja Yunus Ali University, Sirajgonj 6751, BangladeshDepartment of Biotechnology and Genetic Engineering, Islamic University, Kushtia 7003, BangladeshDepartment of Biotechnology and Genetic Engineering, Islamic University, Kushtia 7003, BangladeshDiscipline of Pathology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, AustraliaBone Biology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, AustraliaDiscipline of Pathology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia<i>Background and objectives</i>: 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. <i>Materials and Methods</i>: 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. <i>Results</i>: 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. <i>Conclusions</i>: Protein−drug interaction analysis revealed PDE9A has interaction with drugs caffeine, γ-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.https://www.mdpi.com/1010-660X/55/5/191Alzheimer’s diseaseischemic strokedrug targetsbiomarker signaturesdifferentially expressed genesprotein–protein interactionprotein–drug interactions |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Md. Rezanur Rahman Tania Islam Md. Shahjaman Toyfiquz Zaman Hossain Md. Faruquee Mohammad Abu Hena Mostofa Jamal Fazlul Huq Julian M. W. Quinn Mohammad Ali Moni |
spellingShingle |
Md. Rezanur Rahman Tania Islam Md. Shahjaman Toyfiquz Zaman Hossain Md. Faruquee Mohammad Abu Hena Mostofa Jamal Fazlul Huq Julian M. W. Quinn Mohammad Ali Moni Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic Targets Medicina Alzheimer’s disease ischemic stroke drug targets biomarker signatures differentially expressed genes protein–protein interaction protein–drug interactions |
author_facet |
Md. Rezanur Rahman Tania Islam Md. Shahjaman Toyfiquz Zaman Hossain Md. Faruquee Mohammad Abu Hena Mostofa Jamal Fazlul Huq Julian M. W. Quinn Mohammad Ali Moni |
author_sort |
Md. Rezanur Rahman |
title |
Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic Targets |
title_short |
Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic Targets |
title_full |
Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic Targets |
title_fullStr |
Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic Targets |
title_full_unstemmed |
Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic Targets |
title_sort |
discovering biomarkers and pathways shared by alzheimer’s disease and ischemic stroke to identify novel therapeutic targets |
publisher |
MDPI AG |
series |
Medicina |
issn |
1010-660X |
publishDate |
2019-05-01 |
description |
<i>Background and objectives</i>: 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. <i>Materials and Methods</i>: 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. <i>Results</i>: 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. <i>Conclusions</i>: Protein−drug interaction analysis revealed PDE9A has interaction with drugs caffeine, γ-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. |
topic |
Alzheimer’s disease ischemic stroke drug targets biomarker signatures differentially expressed genes protein–protein interaction protein–drug interactions |
url |
https://www.mdpi.com/1010-660X/55/5/191 |
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