Date of Award
Campus Access Thesis
Master of Science (MS)
Amyloidoses is a group of human diseases characterized by harmful accumulation of misfolded protein aggregates, rich in β-sheet structures referred as amyloids. Alzheimer's disease (AD), the most common neurodegenerative disease, associated with the misfolding of a small peptide called amyloid-beta (Aβ) is often considered to be the archetype of amyloidosis. Several small molecule inhibitors of Aβ self-assembly, that reduce the production of the amyloidogenic form of proteins or increase their clearance rate have been suggested as an attempt to treat amyloidoses.
In the present work we investigated the impact of small organic molecules on self-assembly of Aβ by biochemical, biophysical and imaging techniques. Chalcones and coumarins, diarylhydrazones, phenylhydrazines and carbonyl compounds were selected based on the analysis of literature information on inhibitors of amyloid formation. We further extended our study to investigate the impact of these small molecules on the fibril formation of hen egg white lysozyme (HEWL) to observe if the effect of these compounds displays any similar trends in two distinct amyloidogenic systems.
Our results indicated that these small molecules have significant impact on the self-assembly of Aβ. We have identified new compounds that have resulted in significant decrease in the fibril formation of Aβ. Our preliminary investigations with HEWL suggest that the molecular probes showed similar inhibitory effect on the fibrillogenesis of lysozyme.
Ghosh, Sanjukta, "Investigation of Amyloidogenic Systems by the Application of Small Molecular Probes" (2014). Graduate Masters Theses. 268.