Natural compounds isolated from wild Alaska bog blueberries intervene with molecular targets of neuroinflammation
|Gustafson, Sally Jane
|Dissertation (Ph.D.) University of Alaska Fairbanks, 2010
|NADPH Oxidase (NOX) has emerged as a key mediator of inflammatory processes that are prevalent in acute and chronic pathologies of the nervous system, cardiovascular system, and the immune system. Activation of NOX results in the formation of superoxide, a specific type of reactive oxygen species (ROS). Excessive accumulation of superoxide causes severe oxidative stress and ultimately, progressive cellular damage and degeneration. Despite the implications of NOX in a multitude of pathologies, pharmaceutical interventions against this molecular target remain non-existent. A diet rich in fruits and vegetables has immense health benefits beyond the high content of antioxidant compounds. Dietary intake of blueberries improves age related cognitive deficits and alleviates inflammatory damage as shown through human trials and animal studies. These findings imply that blueberries harbor specific inhibitors against molecular targets implicated in neuronal inflammation. Our investigations unveil natural compounds present in wild Alaska bog blueberries that potently inhibit NOX activity, reduce oxidative stress, and protect neuronal health in a cellular model of neuroinflammation. These studies illuminate nutrition-guided strategies as potential therapies for the prevention and intervention of neurodegeneration and cognitive decline associated with aging and with disease.
|1. NADPH oxidase as a forgotten therapeutic target: the pursuit of free radical regulation -- 2. Design of thesis research -- 3. Alaska wild blueberry extracts inhibit a magnesium-dependent neutral sphingomyelinase activity in neurons exposed to TNFa -- 4. A non-antioxidant compound present in a non-polar blueberry fraction inhibits NADPH oxidase induced neuroinflammation -- 5. Ursolic acid isolated from lipophilic blueberry fraction inhibits NADPH oxidase by lipid raft modulation -- 6. Conclusions and future directions.
|Natural compounds isolated from wild Alaska bog blueberries intervene with molecular targets of neuroinflammation
|Department of Chemistry and Biochemistry
Files in this item
This item appears in the following Collection(s)
Chemistry and Biochemistry
Includes Environmental Chemistry