Preventing the formation of toxic alpha-synuclein oligomers: An alternative therapeutic strategy for slowing the onset of Parkinson's Disease

More than 10 million people worldwide are currently living with Parkinson's disease (PD), and within the US alone, the projected prevalence of PD in the next 15 years will exceed 1.6 million people. There is no cure for PD and current therapeutic strategies targeting the late stages of the disease have been largely unsuccessful. Therefore, the purpose of this proposal is two-fold, namely, to explore a potential avenue of therapeutic development focused on prevention of the disease in its early stages and to better understand the fundamental mechanisms initiating the disease. Research has established a link between amyloid proteins produced by gut bacteria and the exacerbation of PD pathologies in the brain, notably the formation toxic ?-synuclein protein aggregates. Our objectives are to design small molecule inhibitors that specifically shut-off bacterial amyloid production using technology developed in our labs and understand how the interactions between bacterial amyloid and alpha-synuclein proteins leads to the formation of toxic protein aggregates. We expect that the successful completion of this project will not only provide fundamental mechanistic insight into the initiation and progression of PD, but also afford the foundation for the development of broadly applicable, alternative therapeutic strategies for its treatment.

Scholars @ ECU