The Effect of Amyloid-Beta on the Insulin Signalling Pathway in Neuroblastoma 2a (N2a) Cells: The Characterization of Insulin Resistance in Alzheimer’s Disease

FieldValue
dc.contributor.authorYuka, Sai
dc.date.accessioned2016-02-05T13:39:30Z
dc.date.available2018-02-09T09:30:06Z
dc.date.issued2016
dc.identifier.urihttp://hdl.handle.net/10393/34248
dc.identifier.urihttp://dx.doi.org/10.20381/ruor-834
dc.description.abstract7Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by accumulation and deposition of extracellular beta-amyloid peptides (Aβ) and intra-neuronal hyperphosphorylated tau in the brain. The insulin signalling pathway begins upstream at the insulin receptor (IR), where the intracellular insulin receptor substrate 1 (IRS1) is phosphorylated, thus propagating the signal downstream to the PI3K/Akt signalling pathway, which affects both the glycogen synthase kinase 3 beta (GSK3β), which is a tau kinase, and mTOR, which is a critical part of the mTORC1 and mTORC2 complexes that not only mediate a wide range of cell functions, but also feed back upstream to regulate Akt. Increasing evidence builds a strong case for the role of soluble Aβ oligomers (AβOs) in the impairment of insulin signalling in AD. Our in vitro studies with neuroblastoma 2a (N2a) cells stably transfected with human APP695 gene (N2a-APP), which secrete excess Aβ, show that the phosphorylation and expression of several but not all critical signalling proteins along the insulin signalling pathway are dysregulated in the cells in comparison to the parental N2a cells. N2a-APP cells were also found to be phenotypically insulin resistant. Subsequently, N2a-APP cells were treated with the Aβ binding peptide (ABP), which binds Aβ oligomers. The ABP treatment was observed to enhance insulin signalling response compared to untreated controls. The results suggest that Aβ may be responsible for inducing the insulin resistant phenotype in N2a-APP cells, and that the removal of Aβ oligomers is a potential treatment consideration for dysfunctional insulin signalling involved in Alzheimer’s disease.
dc.language.isoen
dc.publisherUniversité d'Ottawa / University of Ottawa
dc.subjectAlzheimer's disease
dc.subjectneurodegeneration
dc.subjectamyloid beta binding protein
dc.subjectcell signalling
dc.subjectamyloid beta
dc.subjectPI3K/Akt
dc.subjectmTOR
dc.titleThe Effect of Amyloid-Beta on the Insulin Signalling Pathway in Neuroblastoma 2a (N2a) Cells: The Characterization of Insulin Resistance in Alzheimer’s Disease
dc.typeThesis
dc.contributor.supervisorLi, Qiao
dc.contributor.supervisorZhang, Wandong
dc.embargo.terms2018-02-09 00:00:00
thesis.degree.nameMSc
thesis.degree.levelMasters
thesis.degree.disciplineMédecine / Medicine
uottawa.departmentMédecine Cellulaire et moléculaire / Cellular and Molecular Medicine
CollectionThèses, 2011 - // Theses, 2011 -

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