Alzheimer's Disease (AD) is a progressive neurodegenerative disease characterized by the formation of insoluble neurotoxic β-amyloid (Aβ) plaques and loss of cognitive function. Plaques have been shown to co-precipitate with both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Interestingly, there is a dramatic increase in BuChE activity relative to AChE in AD patients. Neuroblastoma cells were used to determine the effect of di-n-butyl 2-chlorophenyl phosphate (DBPP), an irreversible inhibitor of BuChE, on formation of Aβ. Cells cultured in 10 μM DBPP accumulated significant amounts of the compound without an effect on cell proliferation, membrane integrity, or induction of apoptosis. The intracellular level of BuChE activity was reduced and there was a decrease in amyloid precursor protein (APP) levels. In contrast, there was a concomitant increase in the levels of both Aβ40 and Aβ42 peptides. The implication is that irreversible inhibition of BuChE activity may increase the rate of Aβ formation.
|Advisor:||Acey, Roger A.|
|Commitee:||McAbee, Douglas, Nakayama, Kensaku|
|School:||California State University, Long Beach|
|Department:||Chemistry and Biochemistry|
|School Location:||United States -- California|
|Source:||MAI 54/04M(E), Masters Abstracts International|
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