Date of Award
Master of Science in Interdisciplinary Neurosciences
Jodi L. Camberg
There are millions of people affected by neurodegenerative diseases worldwide, and currently there is no presented treatment for neurodegenerative disease, and the treatments available are only to stop symptoms or manage disease progress. Therefore, developing a novel treatment or cure for these diseases has become an urgent matter to the world. However, this only happens when there is a deep understanding of the causes and mechanisms of each disease. A pathological hallmark of neurodegenerative diseases is the accumulation of protein aggregates containing an amyloid conformation. These amyloid fibers are comprised of misfolded proteins that are rich in beta-strands and arrange into a stable non-branching fibril through which is difficult to disentangle. On the other hand, amongst the different classes of molecular chaperones, only the yeast heat shock protein Hsp104 has been identified to possess amyloid-disaggregating activity and the ability to reverse fibril formation in vitro. As a result of Hsp104 expression in animal and human cultures, the implication of Hsp104 chaperone as a protein disaggregase could be applied as a therapeutic agent in diseases associated with amyloids and protein aggregation. This thesis investigates the amyloid fiber biology and its management by a heat shock protein (Hsp104). Moreover, we investigate Hsp104 chaperone function in disassembly and clearance of amyloid aggregates in a Saccharomyces cerevisiae (yeast) model system and identify essential amyloid binding regions on the N-terminal domain of Hsp104.
Rahmani, Negar, "ANALYZING HSP104 CHAPERONE FUNCTION IN DISASSEMBLY OF AMYLOID AGGREGATES IN SACCHAROMYCES CEREVISIAE YEAST MODEL SYSTEM" (2021). Open Access Master's Theses. Paper 1991.