The dynamics, energies, and structures governing protein folding are critical to biological function. Amyloidoses are a class of disease defined, in part, by the misfolding and aggregation of functional protein precursors into fibrillar states. Amyloid fibers contribute to the pathology of many diseases, including type II diabetes, Alzheimer's, and Parkinson's. In these disorders, amyloid fibers are present in affected tissues. However, it has become clear that intermediate states, rather than mature fibers, represent the cytotoxic species. In this review, we focus particularly on lipid bilayer–bound intermediates. Remarkably, the precursors of these fibers are intrinsically disordered, and yet catalysis of β-sheet formation appears to be mediated by the stabilization of α-helical states. On the lipid bilayer, these intermediate species have been implicated as cytotoxic through elimination of ionic homeostasis. Recent advances are enabling insights at a molecular level that promise to provide meaningful targets for the development of therapeutics.


Article metrics loading...

Loading full text...

Full text loading...


Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error