See article pre-print here: https://www.biorxiv.org/content/10.1101/2020.05.29.124537v1
We study & discover small molecules that disaggregate amyloid proteins by disrupting ion pairing networks and physically destabilizing protein-protein interfaces.
Amyloid refers to a 3-dimensional fold that can be adopted by almost any protein. The amyloid fold appears in numerous diseases and results in the accumulation of fibrils of misfolded protein. Amyloid diseases often involve misfolding of different proteins, although some proteins can misfold in different ways to form amyloids with different fibril structures--each linked to a different form of disease. Our lab seeks to develop therapies to some of the most intractable amyloid diseases: Alzheimer's, Parkinson's, Multiple systems atrophy (MSA), and ALS by structure-based approaches that allow us to discover and design disaggregants that reverse the amyloid fold.