Observing Development of Amyloid Prefibrillar Intermediates and their Interaction with Chaperones for Inhibiting the Fibril Formation

Abstract

Understanding the mechanism of the amyloid fibril formation is crucial for the development of therapeutic methods of amyloidoses and neurodegenerative diseases. We focused on the role of prefibrillar intermediates that accumulate prior to the fibril formation by using a model peptide derived from insulin. Using circular dichroism spectroscopy, nuclear magnetic resonance, dynamic light scattering, and small-angle X-ray scattering, we found that the fibril formation occurred via specific prefibrillar intermediates. We also found that a plasma protein, fibrinogen, prohibited the fibril formation. It was suggested that the inhibition was exhibited by the specific and strong interaction of fibrinogen with the surface of the prefibrillar intermediates.