Uncovering the mechanisms that regulate β-amyloid aggregation within physiological amyloid-bodies

Author: 
File(s): 
Date created: 
2021-10-05
Identifier: 
etd21730
Supervisor(s): 
Timothy Audas
Department: 
Science: Department of Molecular Biology and Biochemistry
Keywords: 
Alzheimer’s disease
Aggregation
Amyloid bodies
Extracellular stress
Cyclooxygenase pathway
Oxidative stress
Abstract: 

Environmental stress triggers the formation of physiological amyloid-based structures known as A-bodies, which share many biophysical properties with disease-associated plaques. Data indicates that disease-associated proteins, such as β-amyloid, can also aggregate within A-bodies, providing a model system to screen chemical compounds for their ability to regulate physiological and/or pathological amyloid aggregation. In this thesis, I use mammalian cell culture and in vitro aggregation assays to identify drugs that impair β-amyloid targeting/aggregation within A-bodies. My results suggest that compounds capable of inhibiting prostaglandin synthesis (via cyclooxygenase-1 inhibition) or activating oxidative stress pathways can impair β-amyloid aggregation, while having little to no effect on A-body formation. I envisage that the results in this thesis could potentially provide an insight into factors causative for Alzheimer’s disease. Additionally, the data also suggests the existence of a therapeutic window which could be exploited for the impairment of pathological aggregation, without significantly affecting physiological A-body formation.

Thesis type: 
(Thesis) M.Sc.
Document type: 
Thesis
Rights: 
This thesis may be printed or downloaded for non-commercial research and scholarly purposes. Copyright remains with the author.
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