Neutralizing antibodies in Multiple Sclerosis a model-based analysis of Interferon beta signaling pathway in macrophages

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• dc.contributor.author Domingo Espinós, Júlia, 1991-ca
• dc.date.accessioned 2013-09-30T15:15:22Z
• dc.date.available 2013-09-30T15:15:22Z
• dc.date.issued 2013-09-30
• dc.description Treball de fi de grau en Biologia Humanaca
• dc.description Supervisors: Jordi Garcia Ojalvo i/nElena Abad
• dc.description.abstract Multiple Sclerosis is the most common non-traumatic cause of neurological/ndisability in young people. There is no cure yet, and until recently, few long-term/ntherapies existed. Interferon beta (IFNβ) was the first treatment, and remains the most/ncommonly prescribed. One of the most significant problems of IFNβ therapy is the/nproduction of drug specific antibodies. Up to 45% of patients develop neutralizing/nantibodies (NAbs) to IFNβ products. The neutralizing antibody binds to the biological/nagent preventing its interaction with its receptor, inhibiting the biological action of the/nprotein, which abrogates the clinical efficacy of IFNβ treatment. Interferon-beta/nmediates its response by binding to its high affinity cell surface receptor and initiating/nthe JAK/STAT signalling cascade. In this project we have analyzed the IFNβ signaling/npathway in macrophages when neutralizing antibodies are present. The response to/nthis pathway after IFNβ stimulation shows a transient oscillatory rhythm of STAT1/nphosphorylation, which varies as NAbs concentration increases. To improve our/nunderstanding of that behavior, we extended an existing mathematical model based on/nnonlinear ordinary differential equations of JAK/STAT pathway by including IFN-NAb/nassociation and IFN-activation receptor. Combining our theoretical model with/nexperimental data we could study the role of neutralizing antibodies on the molecular/nresponse and determine its lifetime after cytokine stimulation.ca
• dc.format.mimetype application/pdfca
• dc.identifier.uri http://hdl.handle.net/10230/21136
• dc.language.iso engca
• dc.rights © Tots els drets reservats
• dc.rights.accessRights info:eu-repo/semantics/openAccessca
• dc.subject.other Esclerosi múltiple
• dc.subject.other Treball de fi de grau -- Curs 2012-2013
• dc.title Neutralizing antibodies in Multiple Sclerosis a model-based analysis of Interferon beta signaling pathway in macrophagesca
• dc.type info:eu-repo/semantics/bachelorThesisca