Exploring the Molecular Targets for Type 2 Diabetes-Induced Alzheimer’s Disease Through Bioinformatics Analysis

References

• Robb JL , MorrisseyNA , WeightmanPotter PG , SmithersHE , BeallC , EllacottKLJ. Immunometabolic changes in glia – a potential role in the pathophysiology of obesity and diabetes. Neuroscience447, 167–181 (2020).
   PubMed Web of Science ®Google Scholar
• Yan C , ZhouY , ChenQet al. Dysfunction of the neurovascular unit in diabetes-related neurodegeneration. Biomed. Pharmacother.131, 110656 (2020).
   PubMed Web of Science ®Google Scholar
• Muoio V , PerssonPB , SendeskiMM. The neurovascular unit – concept review. Acta Physiol. (Oxf.)210(4), 790–798 (2014).
   PubMed Web of Science ®Google Scholar
• Barbagallo M , DominguezLJ. Type 2 diabetes mellitus and Alzheimer’s disease. World J. Diabetes5(6), 889–893 (2014).
   PubMedGoogle Scholar
• Hayden MR . Type 2 diabetes mellitus increases the risk of late-onset Alzheimer’s disease: ultrastructural remodeling of the neurovascular unit and diabetic gliopathy. Brain Sci.9(10), 262 (2019).
   PubMed Web of Science ®Google Scholar
• Miller JA , WoltjerRL , GoodenbourJM , HorvathS , GeschwindDH. Genes and pathways underlying regional and cell type changes in Alzheimer’s disease. Genome Med.5(5), 48 (2013).
   PubMed Web of Science ®Google Scholar
• Bury JJ , ChambersA , HeathPRet al. Type 2 diabetes mellitus-associated transcriptome alterations in cortical neurones and associated neurovascular unit cells in the ageing brain. Acta Neuropathol. Commun.9(1), 5 (2021).
   PubMed Web of Science ®Google Scholar
• Gautier L , CopeL , BolstadBM , IrizarryRA. affy – analysis of Affymetrix GeneChip data at the probe level. Bioinformatics20(3), 307–315 (2004).
   PubMed Web of Science ®Google Scholar
• Du P , KibbeWA , LinSM. lumi: a pipeline for processing Illumina microarray. Bioinformatics24(13), 1547–1548 (2008).
   PubMed Web of Science ®Google Scholar
• Leek JT , JohnsonWE , ParkerHS , JaffeAE , StoreyJD. The SVA package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics28(6), 882–883 (2012).
   PubMed Web of Science ®Google Scholar
• Zhang B , HorvathS. A general framework for weighted gene co-expression network analysis. Stat. Appl. Genet. Mol. Biol.4, Article17 (2005).
   PubMed Web of Science ®Google Scholar
• Langfelder P , HorvathS. WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics9, 559 (2008).
   PubMed Web of Science ®Google Scholar
• Storey JD , TaylorJE , SiegmundDO. Strong control, conservative point estimation and simultaneous conservative consistency of false discovery rates: a unified approach. J. R. Stat. Soc. Ser. B (Statistical Methodol).66, (2004).
   Web of Science ®Google Scholar
• Smyth GK . limma: linear models for microarray data. In: Bioinformatics and Computational Biology Solutions Using R and Bioconductor.GentlemanR, CareyVJ, HuberW, IrizarryRA, DudoitS ( Eds). Springer New York, NY, USA, 397–420 (2005).
   Google Scholar
• Shannon P , MarkielA , OzierOet al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res.13(11), 2498–2504 (2003).
   PubMed Web of Science ®Google Scholar
• Chin C-H , ChenS-H , WuH-H , HoC-W , KoM-T , LinC-Y. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol.8(Suppl. 4), S11 (2014).
   PubMed Web of Science ®Google Scholar
• Franzén O , GanL-M , BjörkegrenJLM. PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data. Database (Oxford)2019, baz046 (2019).
   PubMedGoogle Scholar
• Jumper J , EvansR , PritzelAet al. Highly accurate protein structure prediction with AlphaFold. Nature596(7873), 583–589 (2021).
   PubMed Web of Science ®Google Scholar
• Bai L , ZhouH , XuRet al. A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo. Cancer Cell36(5), 498–511.e17 (2019).
   PubMed Web of Science ®Google Scholar
• Pierce BG , WieheK , HwangH , KimB-H , VrevenT , WengZ. ZDOCK server: interactive docking prediction of protein–protein complexes and symmetric multimers. Bioinformatics30(12), 1771–1773 (2014).
   PubMed Web of Science ®Google Scholar
• Tang Z , LiC , KangB , GaoG , LiC , ZhangZ. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res.45(W1), W98–W102 (2017).
   PubMed Web of Science ®Google Scholar
• Ho N , SommersMS , LuckiI. Effects of diabetes on hippocampal neurogenesis: links to cognition and depression. Neurosci. Biobehav. Rev.37(8), 1346–1362 (2013).
   PubMed Web of Science ®Google Scholar
• Lok J , GuptaP , GuoSet al. Cell–cell signaling in the neurovascular unit. Neurochem. Res.32(12), 2032–2045 (2007).
   PubMed Web of Science ®Google Scholar
• Hayden MR . Hypothesis: astrocyte foot processes detachment from the neurovascular unit in female diabetic mice may impair modulation of information processing – six degrees of separation. Brain Sci.9(4), 83 (2019).
   PubMed Web of Science ®Google Scholar
• Liu L-R , LiuJ-C , BaoJ-S , BaiQ-Q , WangG-Q. Interaction of microglia and astrocytes in the neurovascular unit. Front. Immunol.11, 1024 (2020).
   PubMed Web of Science ®Google Scholar
• Li X , CaiY , ZhangZ , ZhouJ. Glial and vascular cell regulation of the blood–brain barrier in diabetes. Diabetes Metab. J.46(2), 222–238 (2022).
   PubMed Web of Science ®Google Scholar
• Salameh TS , ShahGN , PriceTO , HaydenMR , BanksWA. Blood–brain barrier disruption and neurovascular unit dysfunction in diabetic mice: protection with the mitochondrial carbonic anhydrase inhibitor topiramate. J. Pharmacol. Exp. Ther.359(3), 452–459 (2016).
   PubMed Web of Science ®Google Scholar
• Biessels GJ , StaekenborgS , BrunnerE , BrayneC , ScheltensP. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol.5(1), 64–74 (2006).
   PubMed Web of Science ®Google Scholar
• Santiago JA , PotashkinJA. The impact of disease comorbidities in Alzheimer’s disease. Front. Aging Neurosci.13, 631770 (2021).
   PubMedGoogle Scholar
• Xue M , XuW , OuY-Net al. Diabetes mellitus and risks of cognitive impairment and dementia: a systematic review and meta-analysis of 144 prospective studies. Ageing Res. Rev.55, 100944 (2019).
   PubMed Web of Science ®Google Scholar
• Sweeney MD , SagareAP , ZlokovicBV. Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat. Rev. Neurol.14(3), 133–150 (2018).
   PubMed Web of Science ®Google Scholar
• Liu LP , HongH , LiaoJMet al. Upregulation of RAGE at the blood–brain barrier in streptozotocin-induced diabetic mice. Synapse63(8), 636–642 (2009).
   PubMed Web of Science ®Google Scholar
• Hong H , LiuLP , LiaoJMet al. Downregulation of LRP1 [correction of LPR1] at the blood–brain barrier in streptozotocin-induced diabetic mice. Neuropharmacology56(6–7), 1054–1059 (2009).
   PubMed Web of Science ®Google Scholar
• Liu H , XuX , YangZ , DengY , LiuX , XieL. Impaired function and expression of P-glycoprotein in blood–brain barrier of streptozotocin-induced diabetic rats. Brain Res.1123(1), 245–252 (2006).
   PubMed Web of Science ®Google Scholar
• Choi M , LeeS-M , KimD , ImH-I , KimH-S , JeongYH. Disruption of the astrocyte–neuron interaction is responsible for the impairments in learning and memory in 5XFAD mice: an Alzheimer’s disease animal model. Mol. Brain14(1), 111 (2021).
   PubMed Web of Science ®Google Scholar
• Spampinato SF , MerloS , SanoY , KandaT , SortinoMA. Astrocytes contribute to Aβ-induced blood–brain barrier damage through activation of endothelial MMP9. J. Neurochem.142(3), 464–477 (2017).
   PubMed Web of Science ®Google Scholar
• van Olst L , VerhaegeD , FranssenMet al. Microglial activation arises after aggregation of phosphorylated-tau in a neuron-specific P301S tauopathy mouse model. Neurobiol. Aging89, 89–98 (2020).
   PubMed Web of Science ®Google Scholar
• Grabert K , MichoelT , KaravolosMHet al. Microglial brain region-dependent diversity and selective regional sensitivities to aging. Nat. Neurosci.19(3), 504–516 (2016).
   PubMed Web of Science ®Google Scholar
• Pinner E , GruperY , BenZimra Met al. CD44 splice variants as potential players in Alzheimer’s disease pathology. J. Alzheimers Dis.58(4), 1137–1149 (2017).
   PubMed Web of Science ®Google Scholar
• Sun J , WuJ , HuaF , ChenY , ZhanF , XuG. Sleep deprivation induces cognitive impairment by increasing blood–brain barrier permeability via CD44. Front. Neurol.11, 563916 (2020).
   PubMed Web of Science ®Google Scholar
• Bozluolcay M , AndicanG , FırtınaS , ErkolG , KonukogluD. Inflammatory hypothesis as a link between Alzheimer’s disease and diabetes mellitus. Geriatr. Gerontol. Int.16(10), 1161–1166 (2016).
   PubMed Web of Science ®Google Scholar
• De Felice FG , FerreiraST. Inflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer disease. Diabetes63(7), 2262–2272 (2014).
   PubMed Web of Science ®Google Scholar
• Kodama K , HorikoshiM , TodaKet al. Expression-based genome-wide association study links the receptor CD44 in adipose tissue with type 2 diabetes. Proc. Natl Acad. Sci. USA109(18), 7049–7054 (2012).
   PubMed Web of Science ®Google Scholar
• Kim S-H , ChoY-S , KimYet al. Endolysosomal impairment by binding of amyloid beta or MAPT/Tau to V-ATPase and rescue via the HYAL–CD44 axis in Alzheimer disease. Autophagy19(8), 2318–2337 (2023).
   PubMed Web of Science ®Google Scholar
• Wan H-L , HongX-Y , ZhaoZ-Het al. STAT3 ameliorates cognitive deficits via regulation of NMDAR expression in an Alzheimer’s disease animal model. Theranostics11(11), 5511–5524 (2021).
   PubMed Web of Science ®Google Scholar
• Yun J-H , LeeD-H , JeongH-S , KimHS , YeS-K , ChoC-H. STAT3 activation in microglia exacerbates hippocampal neuronal apoptosis in diabetic brains. J. Cell. Physiol.236(10), 7058–7070 (2021).
   PubMed Web of Science ®Google Scholar
• Choi M , KimH , YangE-J , KimH-S. Inhibition of STAT3 phosphorylation attenuates impairments in learning and memory in 5XFAD mice, an animal model of Alzheimer’s disease. J. Pharmacol. Sci.143(4), 290–299 (2020).
   PubMed Web of Science ®Google Scholar
• Huang Y , LuJ , ZhaoLet al. Retinal cell-targeted liposomal ginsenoside Rg3 attenuates retinal ischemia–reperfusion injury via alleviating oxidative stress and promoting microglia/macrophage M2 polarization. Free Radic. Biol. Med.206, 162–179 (2023).
   PubMed Web of Science ®Google Scholar
• Das S , LiZ , NooriA , HymanBT , Serrano-PozoA. Meta-analysis of mouse transcriptomic studies supports a context-dependent astrocyte reaction in acute CNS injury versus neurodegeneration. J. Neuroinflammation17(1), 227 (2020).
   PubMed Web of Science ®Google Scholar
• So JY , SmolarekAK , SalernoDMet al. Targeting CD44-STAT3 signaling by Gemini vitamin D analog leads to inhibition of invasion in basal-like breast cancer. PLOS ONE8(1), e54020 (2013).
   PubMed Web of Science ®Google Scholar
• Xu H , NiuM , YuanX , WuK , LiuA. CD44 as a tumor biomarker and therapeutic target. Exp. Hematol. Oncol.9(1), 36 (2020).
   PubMed Web of Science ®Google Scholar
• Weng X , Maxwell-WarburtonS , HasibA , MaL , KangL. The membrane receptor CD44: novel insights into metabolism. Trends Endocrinol. Metab.33(5), 318–332 (2022).
   PubMed Web of Science ®Google Scholar
• Park I-H , LiC. Characterization of molecular recognition of STAT3 SH2 domain inhibitors through molecular simulation. J. Mol. Recognit.24(2), 254–265 (2011).
   PubMedGoogle Scholar
• Sgrignani J , GarofaloM , MatkovicM , MerullaJ , CatapanoCV , CavalliA. Structural biology of STAT3 and its implications for anticancer therapies development. Int. J. Mol. Sci.19(6), 1591 (2018).
   PubMed Web of Science ®Google Scholar
• Lee J-L , WangM-J , ChenJ-Y. Acetylation and activation of STAT3 mediated by nuclear translocation of CD44. J. Cell Biol.185(6), 949–957 (2009).
   PubMed Web of Science ®Google Scholar