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

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.