Amyloid growth and membrane damage: Current themes and emerging perspectives from theory and experiments on Aβ and hIAPP

Abstract

Alzheimer's Disease (AD) and Type 2 diabetes mellitus (T2DM) are two incurable diseases both hallmarked by an abnormal deposition of the amyloidogenic peptides Aβ and Islet Amyloid Polypeptide (IAPP) in affected tissues. Epidemiological data demonstrate that patients suffering from diabetes are at high risk of developing AD, thus making the search for factors common to the two pathologies of special interest for the design of new therapies. Accumulating evidence suggests that the toxic properties of both Aβ or IAPP are ascribable to their ability to damage the cell membrane. However, the molecular details describing Aβ or IAPP interaction with membranes are poorly understood. This review focuses on biophysical and in silico studies addressing these topics. Effects of calcium, cholesterol and membrane lipid composition in driving aberrant Aβ or IAPP interaction with the membrane will be specifically considered. The cross correlation of all these factors appears to be a key issue not only to shed light in the countless and often controversial reports relative to this area but also to gain valuable insights into the central events leading to membrane damage caused by amyloidogenic peptides. This article is part of a Special Issue entitled: Protein Aggregation and Misfolding at the Cell Membrane Interface edited by Ayyalusamy Ramamoorthy.