Abstract 2386 The role of Hsp90 and its accompanying co-chaperones in the folding of proteins and progression of neurodegenerative diseases

The overregulation or overexpression of Hsp90 is linked to the development of cancer and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Studies are currently being conducted to develop synthetic inhibitors of Hsp90 to control its role in the pathogenesis of disease. The family of heat shock proteins are critical for regulation of homeostasis and multiple signaling pathways that control the cell cycle. Heat shock proteins of 90kDa size (Hsp90) act as hydrophobic chaperonins that fold other polypeptides that have either been denatured or need to undergo maturation. They are classified as highly conserved and ubiquitous. Along with its co-chaperonins, Hsp90 orchestrates physiological processes such as apoptosis and hormone signaling. Ultimately, Hsp90 exists as a dimer and is comprised of three structural subunits: an N-terminal, a middle domain, and a C-terminal fragment. The N-terminal domain (NTD) includes an ATP binding motif to facilitate the functioning of Hsp90. A significant co-chaperone, Aha1, stimulates ATPase activity. The middle domain (MD) interacts with many client proteins. There is a charged linker region (CR) located between the NTD and MD increasing the adaptability of Hsp90 in fluctuating environments. The C-terminal domain (CTD) is crucial in acting as a site for allosteric regulatory binding for N-terminal ATPase activity. Our Walton SMART Team, with support from 3-D Molecular Designs, modeled and researched the various aspects of Hsp90. Ultimately, understanding Hsp90 may lead to advancements in treatments of diseases like cancer, Alzheimer's disease, and Parkinson's disease.