Editorial : amyloid-membrane interactions in protein misfolding disorders : from basic mechanisms to therapy

Abstract

It is now well established that the aberrant conversion of peptides or proteins from their native functional states into toxic amyloid entities underlies the pathogenesis of a wide range of debilitating human diseases, collectively known as protein misfolding disorders (PMDs). To date, more than 50 amyloidogenic proteins or peptides have been shown to cause PMDs; these include amyloid-β (Aβ) and tau in Alzheimer’s disease, α-synuclein (α-syn) in Parkinson’s disease, superoxide dismutase 1 (SOD1) in Amyotrophic Lateral Sclerosis, and the human islet amyloid polypeptide (hIAPP) in type2 diabetes mellitus. Accumulating evidence indicates that one of the main pathogenic factors in PMDs involves a direct interaction of amyloidogenic proteins with biomembranes. However, the interplay between the two is highly complex, and overall cytotoxicity depends upon a combination of the physico-chemical properties of the misfolded proteins (e.g., size and surface hydrophobicity) on the one hand, with those of the lipid bilayer (e.g., phospholipid composition, cholesterol and ganglioside content) on the other. Exploring amyloid-membrane interactions at a fundamental level will help inform the development of novel therapeutics for PMDs. In this Research Topic, we have published a collection of five articles dedicated to amyloid-membrane interactions in PMDs, of which three are reviews and two original research articles.