ISSN: 2008-2258
Vol 13, (2020): Supplement1- Winter
Showing NAFLD, as a key connector disease between Alzheimer’s disease and diabetes via analysis of systems biology
Gastroenterology and Hepatology from Bed to Bench,
,
,
Page S89-S97
https://doi.org/10.22037/ghfbb.v13i1.2123
Abstract
Aim: This study was designed to perform network analysis of Alzheimers҆ disease and diabetes and to find their correlation with each other and other diseases/pathways.
Background: Alzheimer’s disease (AD) as a neurodegenerative disease and diabetes as a metabolic disease are two major health problems in the recent years. The recent studies have reported their correlation and same spreading pathways of these two diseases together, but details of this relation are not well known yet at molecular level..
Methods: In thermal proteome profiling (TPP) technique, after treatment of the extracted proteins by heat and drug concentration, the resulting proteins were analyzed by mass spectrometry. Enrichment analysis of these proteins led to development of AD and diabetes. First, corresponding genes for each disease were extracted from DisGeNET database and then, protein-protein interaction network was constructed for each of them using the search tool for retrieval of interacting genes and proteins (STRING). After analyzing these networks, hub-bottleneck nodes of networks were evaluated. Also, common nodes between two networks were extracted and used for further analysis.
Results: High correlation was found between AD and diabetes based on the existence of 40 common genes. Results of analyses revealed 14 genes in AD and 12 genes in diabetes as hub-bottleneck 7 of which were common including caspase 3 (CASP3), insulin-like growth factor 1 (IGF1), catalase (CAT), tumor necrosis factor (TNF), leptin (LEP), vascular endothelial growth factor A (VEGFA), and interleukin 6 ( IL-6).
Conclusion: Our results revealed a direct correlation between AD and diabetes and also a correlation between these two diseases and non-alcoholic fatty liver disease (NAFLD), suggesting that a small change in each of these three diseases can lead to development of any other diseases in the patients. Also, the enrichments exhibited the existence of common pathways between AD, diabetes, NAFLD, and male infertility.
Keywords: NAFLD, Alzheimer's disease, Diabetes mellitus, Type II, Male infertility, Bioinformatics.
(Please cite as: Gholizadeh E, Khaleghian A, Najafgholi Seyfi D, Karbalaei R. Showing NAFLD, as a key connector Disease between Alzheimer’s disease and diabetes via analysis of systems biology. Gastroenterol Hepatol Bed Bench 2020;13(Suppl.1):S89-S97).
- NAFLD
- Alzheimer’s disease
- Diabetes
- Thermal Proteome Profiling
- Male infertility
- Bioinformatics
How to Cite
References
Realdon O, Rossetto F, Nalin M, Baroni I, Cabinio M, Fioravanti R, et al. Technology-enhanced multi-domain at home continuum of care program with respect to usual care for people with cognitive impairment: the Ability-TelerehABILITation study protocol for a randomized controlled trial. BMC Psychiatry 2016;16:425.
Villemagne VL, Burnham S, Bourgeat P, Brown B, Ellis KA, Salvado O, et al. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study. Lancet Neurol 2013;12:357-67.
Reiman EM, Quiroz YT, Fleisher AS, Chen K, Velez-Pardo C, Jimenez-Del-Rio M, et al. Brain imaging and fluid biomarker analysis in young adults at genetic risk for autosomal dominant Alzheimer's disease in the presenilin 1 E280A kindred: a case-control study. Lancet Neurol 2012;11:1048-56.
Gordon BA, Blazey TM, Su Y, Hari-Raj A, Dincer A, Flores S, et al. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer's disease: a longitudinal study. Lancet Neurol 2018;17:241-50.
Alzheimer’s Association. 2019 Alzheimer's disease facts and figures. Alzheimers Dement 2019;15:321-87.
Ghareeb DA, Hafez HS, Hussien HM, Kabapy NF. Non-alcoholic fatty liver induces insulin resistance and metabolic disorders with development of brain damage and dysfunction. Metab Brain Dis 2011;26:253.
Reddy JK, Sambasiva Rao M. Lipid metabolism and liver inflammation. II. Fatty liver disease and fatty acid oxidation. Am J Physiol Gastrointest Liver Physiol 2006;290:G852-8.
Punthakee Z, Goldenberg R, Katz P. Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome. Can J Diabetes 2018;42:S10-5.
Raisifar Z, Nia AA, Madmoli M, Madmoli Y. The relationship between using insulin and suffering Alzheimer's disease in patients with diabetes: a two-year study. International Journal of Ecosystems and Ecology Science (IJEES) 2018;8:623-8.
Thomas KR, Bangen KJ, Weigand AJ, Edmonds EC, Sundermann E, Wong CG, et al. Type 2 Diabetes Interacts With Alzheimer Disease Risk Factors to Predict Functional Decline. Alzheimer Dis Assoc Disord 2020;34:10-7.
Li J, Cesari M, Liu F, Dong B, Vellas B. Effects of diabetes mellitus on cognitive decline in patients with Alzheimer disease: a systematic review. Can J Diabetes 2017;41:114-9.
Arnold SE, Arvanitakis Z, Macauley-Rambach SL, Koenig AM, Wang H-Y, Ahima RS, et al. Brain insulin resistance in type 2 diabetes and Alzheimer disease: concepts and conundrums. Nat Rev Neurol 2018;14:168-81.
Jafari R, Almqvist H, Axelsson H, Ignatushchenko M, Lundbäck T, Nordlund P, et al. The cellular thermal shift assay for evaluating drug target interactions in cells. Nat Protoc 2014;9:2100.
Savitski MM, Reinhard FB, Franken H, Werner T, Savitski MF, Eberhard D, et al. Tracking cancer drugs in living cells by thermal profiling of the proteome. Science 2014;346:1255784.
Dembo G, Park SB, Kharasch ED. Central nervous system concentrations of cyclooxygenase-2 inhibitors in humans. Anesthesiology-Hagerstown 2005;102:409-15.
Paulson SK, Vaughn MB, Jessen SM, Lawal Y, Gresk CJ, Yan B, et al. Pharmacokinetics of celecoxib after oral administration in dogs and humans: effect of food and site of absorption. J Pharmacol Exp Ther 2001;297:638-45.
Wiśniewski JR, Zougman A, Nagaraj N, Mann M. Universal sample preparation method for proteome analysis. Nat Methods 2009;6:359-62.
Scifo E, Szwajda A, Soliymani R, Pezzini F, Bianchi M, Dapkunas A, et al. Proteomic analysis of the palmitoyl protein thioesterase 1 interactome in SH-SY5Y human neuroblastoma cells. J Proteomics 2015;123:42-53.
Piñero J, Bravo À, Queralt-Rosinach N, Gutiérrez-Sacristán A, Deu-Pons J, Centeno E, et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res 2017;45:D833-39.
Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, et al. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res 2017;45:D362-68.
Nepusz T, Yu H, Paccanaro A. Detecting overlapping protein complexes in protein-protein interaction networks. Nat Methods 2012;9:471.
Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 2009;25:1091-3.
Bindea G, Galon J, Mlecnik B. CluePedia Cytoscape plugin: pathway insights using integrated experimental and in silico data. Bioinformatics 2013;29:661-3.
Ashtiani M, Mirzaie M, Jafari M. CINNA: An R package for deciphering Central Informative Nodes in Network Analysis. bioRxiv 2017:168757.
Ashtiani M, Salehzadeh-Yazdi A, Razaghi-Moghadam Z, Hennig H, Wolkenhauer O, Mirzaie M, et al. Selection of most relevant centrality measures: A systematic survey on protein-protein interaction networks. bioRxiv 2017:149492.
Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003;13:2498-504.
Hunter DJ. Gene–environment interactions in human diseases. Nat Rev Genet 2005;6:287-98.
Du S, Maneix L, Zhang Q, Wan YW, Zheng H. The role of FOXO3 transcription factor in Alzheimer’s disease pathology. Innov Aging 2019;3:S842.
Cao P, Maximov A, Südhof TC. Activity-dependent IGF-1 exocytosis is controlled by the Ca(2+)-sensor synaptotagmin-10. Cell 2011;145:300-11.
Li Z-g, Zhang W, Sima AA. Alzheimer-like changes in rat models of spontaneous diabetes. Diabetes 2007;56:1817-24.
Zhao X, Bausano B, Pike BR, Newcomb-Fernandez JK, Wang KK, Shohami E, et al. TNF‐α stimulates caspase‐3 activation and apoptotic cell death in primary septo‐hippocampal cultures. J Neurosci Res 2001;64:121-31.
Holmes C, Cunningham C, Zotova E, Woolford J, Dean C, Kerr Su, et al. Systemic inflammation and disease progression in Alzheimer disease. Neurology 2009;73:768-74.
Zali MR, Rostami Nejad M, Rostami K, Alavian SM. Liver complications in celiac disease. Hepat Mon. 2011;11:333-41.
Mejido DC, Andrade J, Vieira MN, Ferreira ST, De Felice FG. Insulin and leptin as potential cognitive enhancers in metabolic disorders and Alzheimer's disease. Neuropharmacology 2020:108115.
Meek TH, Morton GJ. The role of leptin in diabetes: metabolic effects. Diabetologia 2016;59:928-32.
Jiang LQ, Duque-Guimaraes DE, Machado UF, Zierath JR, Krook A. Altered response of skeletal muscle to IL-6 in type 2 diabetic patients. Diabetes 2013;62:355-61.
Alizadeh AH, Ranjbar M, Ansari S, MirArab A, Alavian SM, Mohammad K, et al. Seroprevalence of hepatitis B in Nahavand, Islamic Republic of Iran. East Mediterr Health J 2006;12:528-37.
Sawada M, Imamura K, Nagatsu T. Role of cytokines in inflammatory process in Parkinson's disease. J Neural Transm Suppl 2006;70:373-81.
Mirza Z, A Kamal M, H Al-Qahtani M, Karim S. Establishing genomic/transcriptomic links between Alzheimer’s disease and type 2 diabetes mellitus by meta-analysis approach. CNS Neurological Disorders-Drug Targets 2014;13:501-16.
Tischer E, Mitchell R, Hartman T, Silva M, Gospodarowicz D, Fiddes J, et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 1991;266:11947-54.
Jafari F, Hamidian M, Rezadehbashi M, Doyle M, Salmanzadeh-Ahrabi S, Derakhshan F, et al. Prevalence and antimicrobial resistance of diarrheagenic Escherichia coli and Shigella species associated with acute diarrhea in Tehran, Iran. Can J Infect Dis Med Microbiol 2009;20:e56-62.
Chiappelli M, Borroni B, Archetti S, Calabrese E, Corsi MM, Franceschi M, et al. VEGF gene and phenotype relation with Alzheimer's disease and mild cognitive impairment. Rejuven Res 2006;9:485-93.
Karbalaei R, Allahyari M, Rezaei-Tavirani M, Asadzadeh-Aghdaei H, Zali MR. Protein-protein interaction analysis of Alzheimers disease and NAFLD based on systems biology methods unhide common ancestor pathways. Gastroenterol Hepatol Bed Bench 2018;11:27.
Ahmad A, Ali T, Kim MW, Khan A, Jo MH, Rehman SU, et al. Adiponectin homolog novel osmotin protects obesity/diabetes-induced NAFLD by upregulating AdipoRs/PPARα signaling in ob/ob and db/db transgenic mouse models. Metabolism 2019;90:31-43.
Lee CH, Olson P, Hevener A, Mehl I, Chong LW, Olefsky JM, et al. PPARδ regulates glucose metabolism and insulin sensitivity. Proc Natl Acad Sci Unit States Am 2006;103:3444-9.
Huang W, Metlakunta A, Dedousis N, Zhang P, Sipula I, Dube JJ, et al. Depletion of liver Kupffer cells prevents the development of diet-induced hepatic steatosis and insulin resistance. Diabetes 2010;59:347-57.
Younossi ZM, Golabi P, de Avila L, Paik JM, Srishord M, Fukui N, et al. The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis. J Hepatol 2019;71:793-801.
Yaffe K, Falvey C, Hamilton N, Schwartz AV, Simonsick EM, Satterfield S, et al. Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia. Arc Neurol 2012;69:1170-5.
Roberts RO, Knopman DS, Geda YE, Cha RH, Pankratz VS, Baertlein L, et al. Association of diabetes with amnestic and nonamnestic mild cognitive impairment. Alzheimer's Dementia 2014;10:18-26.
Ford W. Glycolysis and sperm motility: does a spoonful of sugar help the flagellum go round? Hum Reprod Update 2006;12:269-74.
Miki K. Energy metabolism and sperm function. Soc Reprod Fertil Suppl 2007;65:309-25.
Flesch FM, Gadella BM. Dynamics of the mammalian sperm plasma membrane in the process of fertilization. Biochim Biophys Acta 2000;1469:197-235.
Zali MR, Mohammad K, Noorbala AA, Noorimayer B, Shahraz S. Rate of hepatitis B seropositivity following mass vaccination in the Islamic Republic of Iran. East Mediterr Health J 2005;11:62-7.
Beeram E, Suman B, Divya B. Proteins as the Molecular Markers of Male Fertility. J Hum Reprod Sci 2019;12:19-23.
López-Lemus UA, Garza-Guajardo R, Barboza-Quintana O, Rodríguez-Hernandez A, García-Rivera A, Madrigal-Pérez VM, et al. Association between nonalcoholic fatty liver disease and severe male reproductive organ impairment (germinal epithelial loss): Study on a mouse model and on human patients. Am J Mens Health 2018;12:639-48.
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