Ceramide Metabolism Regulates A Neuronal Nadph Oxidase Influencing Neuron Survival During Inflammation
dc.contributor.author | Barth, Brian M. | |
dc.date.accessioned | 2018-08-06T22:37:29Z | |
dc.date.available | 2018-08-06T22:37:29Z | |
dc.date.issued | 2009 | |
dc.identifier.uri | http://hdl.handle.net/11122/8999 | |
dc.description | Dissertation (Ph.D.) University of Alaska Fairbanks, 2009 | |
dc.description.abstract | Inflammation is a major component of acute and chronic pathologies of the central nervous system, including psychiatric disorders. Microglia respond to pathogens, injury, and toxins by secreting inflammatory mediators including pro-inflammatory cytokines in an event known as neuroinflammation. This thesis research investigated a link between neuroinflammation and oxidative stress, and ultimately neurodegeneration. The cytokine tumor necrosis factor alpha was shown to stimulate a neuronal NADPH oxidase (NOX), specifically by stimulating the production of ceramide and ceramide-1-phosphate via Mg 2+-neutral sphingomyelinase (Mg2+-nSMase) and ceramide kinase. Intriguingly, glucosylceramide blocked NOX activation, linking ceramide neutralization directly to a decline in oxidative stress. Most importantly, NOX activity interfered with actin and sphingosine kinase-1 via oxidation, demonstrating a positive and detrimental feedback mechanism that impedes neuronal survival pathways. Interestingly, crude extracts from wild Alaskan bog blueberries showed the ability to interfere with Mg2+-nSMase, demonstrating a specific neuroprotective property of the berry. Altogether, this thesis research defined a key neuronal pathway linking inflammation to oxidative stress via ceramide metabolism, potentially allowing for future therapeutic development to improve neuronal function and survival. | |
dc.subject | Biochemistry | |
dc.subject | Neurosciences | |
dc.subject | Molecular biology | |
dc.title | Ceramide Metabolism Regulates A Neuronal Nadph Oxidase Influencing Neuron Survival During Inflammation | |
dc.type | Dissertation | |
dc.type.degree | phd | |
dc.identifier.department | Department of Chemistry and Biochemistry | |
refterms.dateFOA | 2020-03-06T01:04:37Z |
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Chemistry and Biochemistry
Includes Environmental Chemistry