Targeting Connexins to Promote Functional Neural Repair and Regeneration

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dc.contributor.authorCooke, Donald M.
dc.date.accessioned2013-07-10T17:55:55Z
dc.date.available2015-07-11T08:00:07Z
dc.date.created2013
dc.date.issued2013-07-10
dc.identifier.urihttp://hdl.handle.net/10393/24308
dc.identifier.urihttp://dx.doi.org/10.20381/ruor-6717
dc.description.abstractThe connexins are a family of 21 proteins that represent the structural units of intercellular gap junctions and single membrane hemichannels. These channels provide a means for cells to exchange small metabolites and signaling molecules with adjacent cells and the extracellular space, respectively. Compelling evidence implicates connexins, and the more recently discovered pannexins, in the control of neural progenitor cell proliferation, survival and migration. Moreover, connexin and pannexin dysregulation following central nervous system injuries such as cerebral ischemia, spinal cord injury, and epilepsy contributes to the secondary expansion of lesions days and weeks after the initial insult. While these data suggest that connexins and pannexins represent novel therapeutic targets to both reduce the extent of neural injury and promote neural repair and regeneration, we currently lack the necessary repertoire of therapeutically useful connexin- and pannexin-specific compounds to test these hypotheses. In this thesis, I conducted targeted screening of a large, ethnobotanically-derived library to address my overarching objective of identifying compounds that selectively alter connexin and/or pannexin channel function. To accomplish this, I characterized the repertoire of connexins and pannexins expressed by neural progenitor cell-like NT2/D1 cells, quantified the intercellular flux of calcein through connexin gap junctions, and measured the uptake of lucifer yellow and propidium iodide through pannexin hemichannels. Collectively, these screens identified several promising lead compounds and ethanolic plant extracts that selectively alter connexin and pannexin channel activity.
dc.language.isoen
dc.publisherUniversité d'Ottawa / University of Ottawa
dc.subjectGap junctions
dc.subjectConnexins
dc.subjectPannexins
dc.subjectDrug discovery
dc.titleTargeting Connexins to Promote Functional Neural Repair and Regeneration
dc.typeThesis
dc.contributor.supervisorBennett, Steffany AL
dc.contributor.supervisorTsai, EC
dc.contributor.supervisorCao, X
dc.embargo.terms2 years
thesis.degree.nameMSc
thesis.degree.levelMasters
thesis.degree.disciplineMédecine / Medicine
uottawa.departmentBiochimie, microbiologie et immunologie / Biochemistry, Microbiology and Immunology
CollectionThèses, 2011 - // Theses, 2011 -

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