Aggregation Inhibition and Detection of Alzheimer’s Amyloidogenic and Oligomeric Peptides

Protein aggregation, oligomer and fibril formation is one of the dominant
characteristics in the pathogenesis of a number of neurodegenerative diseases, such as
Alzheimer’s disease (AD). Inhibition of toxic oligomer and fibril formation is one of
the approaches to find potential drug candidates for AD. Additionally, early diagnosis
of these amyloid species can provide mechanistic understanding of protein aggregation
and thus can pave the way for preventing the onset of AD. The aim of this dissertation
was 1) to explore the effects of charged cholesterol derivatives on the aggregation
kinetic behavior of Amyloid-β40 (Aβ40), 2) to probe Aβ40 oligomer and amyloid
formation in vitro using gold nanoparticles (AuNPs), and 3) to monitor the kinetic
effect of various natural product molecules on Aβ40 aggregation in vitro. In the first
chapter, a general introduction about AD as an amyloidogenic disease, amyloid cascade
hypothesis, and the manipulation of Aβ peptides aggregation kinetics using different
approaches was presented. In the second chapter, we studied the effects of oppositely charged cholesterol derivatives on the aggregation kinetics of Aβ. In the third chapter,
we developed a gold nanoparticles (AuNPs) assay to probe Aβ40 oligomers and
amyloid formation. In chapter IV, we monitored the effects of various small molecules
on the aggregation kinetics of Aβ40. In chapter V, we discussed the methods and
experimental details.