Date Approved

2023

Degree Type

Campus Only Thesis

Degree Name

Master of Science (MS)

Department or School

Chemistry

Committee Member

Hedeel Evans, Ph.D., Chair

Committee Member

Jeffrey Guthrie, Ph.D.

Committee Member

Ruth Armitage, Ph.D.

Committee Member

Deborah Heyl-Clegg, Ph.D.

Abstract

Previous studies in our lab found that media from H1299 cells have lower levels of acetylcholinesterase (AChE) and intact amyloid-β40/42 (Aβ), and higher levels of mature brain-derived neurotrophic factor (mBDNF) when compared to A549 cell media. In conjunction to this the levels of soluble amyloid precursor protein α (sAPPα) were higher in H1299 cell media compared to A549 cell media. With these previous findings, we hypothesize that the levels of sAPPα are regulated by AChE and mBDNF. When cells were treated with AChE, sAPPα levels were decreased while Aβ levels increased which suggests that AChE might play a role in shifting APP processing towards the amyloidogenic pathway and away from the non-amyloidogenic pathway. Conversely, treatment with mBDNF leads to higher sAPPα levels and lower Aβ levels in the cell media. Knockdown of AChE led to lower levels of Aβ and increased the levels of sAPPα and mBDNF in the cell media. AChE and mBDNF both operated through a mechanism involving α-secretase activity and were found to have opposite effects on the levels of sAPPα and Aβ. sAPPα levels were also found to be regulated by protein kinase C (PKC), extracellular signal-regulated kinase (ERK) 1/2, phosphoinositide 3 kinase (PI3K), but not protein kinase A (PKA).

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