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Process Model of Herpes Simplex Virus I-Induced Activation of Toll-like Receptor 2 Mediated Microglial Signaling in the Inflammatory Pathogenesis of Alzheimer’s Disease
Jones, Catherine
Jones, Catherine
Abstract
Alzheimer’s disease (AD) is a neurodegenerative disease causing the progressive loss of memory and cognitive function. AD is characterized by amyloid beta (Aβ ) aggregation and chronic neuroinflammation. Recent research reframes AD as a result of a dysregulated immune response to viral infection of the central nervous system. The present thesis explores this hypothesis. Herpes simplex virus-1 (HSV-1) mediated activation of the Toll-like receptor 2 (TLR2) inflammatory pathway in microglia was computationally modeled using CellDesigner 4.2. The model was run through SBML Squeezer, which assigned mathematical equations to the reactions in the model. Then, time course data of species concentration over time was obtained by COPASI. Results showed that the model accurately reflected the pathway as qualitatively described in the literature, namely that nuclear factor kappa beta (NF-KB) becomes sequestered in the nucleus by HSV-1 viral protein ICP0 which allows for the dysregulated chronic transcription and translation of proinflammatory cytokines.
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2022-05-01
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Neuroscience
