Alzheimer’s disease (AD) is a fatal neurodegenerative disease affecting 5.5 million Americans. Despite many decades of research there is still no known cure. AD is a protein misfolding disease, where the Alzheimer’s protein, Aβ, aggregates from a random coil entity into fibrils, which are highly organized aggregates containing a cross-β sheet structure. However, the nature of the toxic species in Alzheimer’s disease remains unknown. Nature has developed mechanisms to prevent disease-associated protein aggregation, e.g. by the introduction of heat shock proteins (Hsp's), which are overexpressed when cells undergo stress. Hsp60 is the only essential chaperone in bacteria, yeast, and mammals. It is known that Hsp60 is cytoprotective against many stressors in cells and is proposed to be directly protective against AD. However, nothing is known about the mechanism of how this is achieved. 

We will be using a variety of biochemical assays to investigate how Hsp60 interacts with the Alzheimer’s peptide with a focus on solution-state NMR and cryo-electron microscopy. These studies will provide insights into fundamental questions about the mechanism chaperones use to efficiently fold proteins into their functional forms. Further the results will unveil details about how Hsp60 inhibits the aggregation of the Alzheimer’s peptide and prevents neurodegenerative disease and may open up novel therapeutic strategies against Alzheimer’s disease.