Research – Investigations of Receptor Mediated Neurodegeneration

As research in human neurodegeneration has moved from descriptive phenomenology to mechanistic analysis, it has become vitally important provide detailed structural and functional input into the origins and mechanisms of amyloid diseases. For the case of Alzheimer’s disease, we are working in collaboration with a group at Northwestern University led by Professors William Kline to understand the biochemical mechanism by which soluble oligomers of Aß peptide (AβOs) bind to synaptic plasma membranes and cause the early memory loss. Currently it is unknown whether AβOs bind to specific receptors or bind non-specifically to various receptors and channel proteins. Using the Nanodisc technology, we developed a means to generate soluble membrane protein libraries (SMPLs) of any starting tissue wherein each membrane protein is assembled into an individual Nanodisc. Using this approach we can identify synaptosomal receptor targets of AβOs and develop high throughput screening assays to reveal potential pharmaceuticals for therapeutic intervention. A start-up company SMPL Solutions LLC has been formed in Chicago to commercialize this approach.