A New Method to Determine Alzheimer's and Parkinson's Toxins in the Lipid-Riched Environment

In diseases such as Alzheimer’s and Parkinson’s, toxic protein lumps form holes in them nerve cells. I want to discover how those lumps assemble at atomic resolution.

In Alzheimer’s disease, Aβ peptides form toxic and transient oligomers, leading to cellular membrane leakage and then neuronal cell death. We aim to stabilize the transient oligomers on a functionally relevant α-hemolysin (αHL) scaffold and confine the stabilized/hybridized oligomers for crystallization in the lipidic cubic phase system followed by X-ray structure determination. The hybridized Aβ oligomers will allow studying many of the features of amyloid oligomers that can not be characterized due to the transient and heterogeneity of wild-type Aβ oligomers. Our work will yield essential insight into the mechanism of its neurotoxicity.