Master of Science (M.S.)
Degree Granting Department
Umesh Jinwal, Ph.D.
Feng Cheng, Ph.D.
Vijaykumar Sutariya, Ph.D.
Chaperone proteins, Drug discovery, Neurodegenerative diseases, Hsp90/Cdc37 Complex
Neurodegenerative disease refers to the death of specific populations of neurons that canresult in dementia, loss of voluntary muscle motility, and other abnormalities. Two major neurodegenerative diseases are Alzheimer’s disease (AD) and Parkinson’s disease (PD), which are linked to abnormalities in Tau and a-synuclein proteins, respectively. Currently, there is no cure for these diseases. Our group and others have shown that chaperone proteins play a critical role in the processing of Tau and a-synuclein. The inhibition of the Hsp90/Cdc37 chaperone complex is shown to affect the levels of these two proteins. Hence, we hypothesized that a drug molecule, conglobatin (Cb), that has been shown to disrupt this interface will lead to clearance of Tau and a-synuclein. The objective of this study was to test the effect of Cb on the levels of pathogenic neurodegenerative proteins using an in vitro model. M17 neuronal cells stably overexpressing wildtype a-synuclein were treated with increasing doses of Cb. These cells also express detectable levels of endogenous Tau protein. After 24 hours of drug treatment with Cb, the cells were lysed and processed for the western blot analysis using Tau and a-synuclein antibodies. Western blots were quantified using Scion Image software and statistical analysis was performed using GraphPad Prism 9. Data analysis showed that Cb drug cleared Tau and asynuclein effectively. These results validate our hypothesis. Further mechanistic and animal studies are needed to establish this drug as a viable candidate for the treatment of AD, PD, and potentially for other related neurodegenerative disorder
Scholar Commons Citation
Martin, Ryan, "Drug Candidates Targeting Hsp90/Cdc37 for the Treatment of Neurodegenerative Disease" (2021). USF Tampa Graduate Theses and Dissertations.