Exploring the common pathogenesis of Alzheimer's disease and type 2 diabetes mellitus
Alzheimer’s disease
bioinformatics analysis
network pharmacology
pathophysiological mechanisms
type 2 diabetes mellitus
Journal
Frontiers in aging neuroscience
ISSN: 1663-4365
Titre abrégé: Front Aging Neurosci
Pays: Switzerland
ID NLM: 101525824
Informations de publication
Date de publication:
2023
2023
Historique:
received:
16
10
2022
accepted:
03
02
2023
entrez:
16
3
2023
pubmed:
17
3
2023
medline:
17
3
2023
Statut:
epublish
Résumé
Alzheimer's Disease (AD) and Type 2 Diabetes Mellitus (DM) have an increased incidence in modern society. Although more and more evidence has supported that DM is prone to AD, the interrelational mechanisms remain fully elucidated. The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and DM. Download the expression matrix of AD and DM from the Gene Expression Omnibus (GEO) database with sequence numbers GSE97760 and GSE95849, respectively. The common differentially expressed genes (DEGs) were identified by limma package analysis. Then we analyzed the six kinds of module analysis: gene functional annotation, protein-protein interaction (PPI) network, potential drug screening, immune cell infiltration, hub genes identification and validation, and prediction of transcription factors (TFs). The subsequent analyses included 339 common DEGs, and the importance of immunity, hormone, cytokines, neurotransmitters, and insulin in these diseases was underscored by functional analysis. In addition, serotonergic synapse, ovarian steroidogenesis, estrogen signaling pathway, and regulation of lipolysis are closely related to both. DEGs were input into the CMap database to screen small molecule compounds with the potential to reverse AD and DM pathological functions. L-690488, exemestane, and BMS-345541 ranked top three among the screened small molecule compounds. Finally, 10 essential hub genes were identified using cytoHubba, including The common pathogenesis of AD and DM was revealed in our research. These common pathways and hub genes directions for further exploration of the pathogenesis or treatment of these two diseases.
Sections du résumé
Background
UNASSIGNED
Alzheimer's Disease (AD) and Type 2 Diabetes Mellitus (DM) have an increased incidence in modern society. Although more and more evidence has supported that DM is prone to AD, the interrelational mechanisms remain fully elucidated.
Purpose
UNASSIGNED
The primary purpose of this study is to explore the shared pathophysiological mechanisms of AD and DM.
Methods
UNASSIGNED
Download the expression matrix of AD and DM from the Gene Expression Omnibus (GEO) database with sequence numbers GSE97760 and GSE95849, respectively. The common differentially expressed genes (DEGs) were identified by limma package analysis. Then we analyzed the six kinds of module analysis: gene functional annotation, protein-protein interaction (PPI) network, potential drug screening, immune cell infiltration, hub genes identification and validation, and prediction of transcription factors (TFs).
Results
UNASSIGNED
The subsequent analyses included 339 common DEGs, and the importance of immunity, hormone, cytokines, neurotransmitters, and insulin in these diseases was underscored by functional analysis. In addition, serotonergic synapse, ovarian steroidogenesis, estrogen signaling pathway, and regulation of lipolysis are closely related to both. DEGs were input into the CMap database to screen small molecule compounds with the potential to reverse AD and DM pathological functions. L-690488, exemestane, and BMS-345541 ranked top three among the screened small molecule compounds. Finally, 10 essential hub genes were identified using cytoHubba, including
Conclusion
UNASSIGNED
The common pathogenesis of AD and DM was revealed in our research. These common pathways and hub genes directions for further exploration of the pathogenesis or treatment of these two diseases.
Identifiants
pubmed: 36923118
doi: 10.3389/fnagi.2023.1071391
pmc: PMC10008874
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1071391Informations de copyright
Copyright © 2023 Ye, Liu, Wang, Cheng, Li, Bai, Yang, Wang, Wen, Xu, Zhang, Xu and Li.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Commun Biol. 2021 Sep 3;4(1):1036
pubmed: 34480097
BMC Genomics. 2012 Feb 27;13:81
pubmed: 22369239
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
Nat Genet. 2011 May;43(5):429-35
pubmed: 21460840
Mol Genet Metab. 2013 May;109(1):112-7
pubmed: 23499280
Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):E2077-82
pubmed: 22711829
J Alzheimers Dis. 2015;43(1):93-108
pubmed: 25079797
Curr Med Sci. 2021 Dec;41(6):1165-1171
pubmed: 34874485
Lancet Neurol. 2008 Jul;7(7):583-90
pubmed: 18539534
J Cell Sci. 2009 Jun 1;122(Pt 11):1713-21
pubmed: 19461071
Nat Genet. 2013 Dec;45(12):1452-8
pubmed: 24162737
Front Pharmacol. 2020 Sep 08;11:564131
pubmed: 33013400
Adv Exp Med Biol. 2019;1128:45-83
pubmed: 31062325
J Neurosci. 2002 Sep 15;22(18):7931-40
pubmed: 12223546
PLoS Comput Biol. 2014 Jul 24;10(7):e1003731
pubmed: 25058159
Am J Transl Res. 2021 Oct 15;13(10):11316-11328
pubmed: 34786060
Neuromolecular Med. 2014 Mar;16(1):150-60
pubmed: 24101586
Neurochem Int. 2018 Oct;119:35-41
pubmed: 28697973
Brain Imaging Behav. 2021 Jun;15(3):1155-1169
pubmed: 32803660
Saudi J Biol Sci. 2020 Feb;27(2):736-750
pubmed: 32210695
J Neurochem. 2021 Mar;156(6):753-776
pubmed: 32909269
Int J Mol Sci. 2021 Nov 03;22(21):
pubmed: 34769364
Cell. 2017 Nov 30;171(6):1437-1452.e17
pubmed: 29195078
Drug Dev Ind Pharm. 2021 Aug;47(8):1279-1289
pubmed: 34605344
Life (Basel). 2021 Aug 09;11(8):
pubmed: 34440550
Diabetes. 2014 Sep;63(9):3009-21
pubmed: 24740569
Br J Cancer. 2021 Jan;124(1):66-75
pubmed: 33262521
Int J Mol Sci. 2021 Nov 15;22(22):
pubmed: 34830192
BMC Complement Med Ther. 2020 Apr 28;20(1):130
pubmed: 32345291
Front Immunol. 2021 May 27;12:667690
pubmed: 34122426
Biochim Biophys Acta Mol Basis Dis. 2017 May;1863(5):1078-1089
pubmed: 27567931
Nucleic Acids Res. 2010 Jul;38(Web Server issue):W214-20
pubmed: 20576703
J Diabetes Investig. 2013 Nov 27;4(6):640-50
pubmed: 24843720
Mol Neurobiol. 2017 Dec;54(10):7994-8008
pubmed: 27878759
Neurosci Biobehav Rev. 2016 May;64:272-87
pubmed: 26969101
Diab Vasc Dis Res. 2018 Mar;15(2):158-161
pubmed: 29233017
World J Diabetes. 2021 Jun 15;12(6):745-766
pubmed: 34168725
Front Aging Neurosci. 2022 Jun 21;14:890046
pubmed: 35795239
J Alzheimers Dis. 2018;62(3):1381-1390
pubmed: 29562538
Ageing Res Rev. 2019 Sep;54:100936
pubmed: 31330313
Alzheimers Dement. 2018 Jul;14(7):848-857
pubmed: 29494809
PLoS One. 2015 Mar 20;10(3):e0120742
pubmed: 25793868
Clin Interv Aging. 2018 Dec 28;14:73-79
pubmed: 30643396
Front Genet. 2021 Jul 01;12:658323
pubmed: 34276768
Cells. 2021 May 18;10(5):
pubmed: 34069890
Biochim Biophys Acta Mol Basis Dis. 2017 May;1863(5):1037-1045
pubmed: 27156888
Int J Mol Sci. 2018 Oct 24;19(11):
pubmed: 30355995
J Neurol Sci. 2017 Sep 15;380:262-272
pubmed: 28870582
Curr Alzheimer Res. 2020;17(6):566-575
pubmed: 32781959
J Diabetes Res. 2017;2017:8103904
pubmed: 28900628
J Alzheimers Dis. 2020;74(4):1295-1308
pubmed: 32250298
Front Pharmacol. 2021 Feb 12;11:609825
pubmed: 33643040
FASEB J. 2019 Jan;33(1):13-33
pubmed: 30020833