An increasing number of human diseases has been shown to be linked to aggregation and amyloid formation by intrinsically disordered proteins (IDPs). Amylin, amyloid-β, and α-synuclein are, indeed, involved in type-II diabetes, Alzheimer's, and Parkinson's, respectively. Despite the correlation of the toxicity of these proteins at early aggregation stages with membrane damage, the molecular events underlying the process is quite complex to understand. In this study, we demonstrate the crucial role of free lipids in the formation of lipid-protein complex, which enables an easy membrane insertion for amylin, amyloid-β, and α-synuclein. Experimental results from a variety of biophysical methods and molecular dynamics results reveal that this common molecular pathway in membrane poration is shared by amyloidogenic (amylin, amyloid-β, and α-synuclein) and nonamyloidogenic (rat IAPP, β-synuclein) proteins. Based on these results, we propose a "lipid-chaperone" hypothesis as a unifying framework for protein-membrane poration.

• Keywords
• Alzheimer, Intrinsically disordered proteins, Parkinson, diabetes mellitus, lipid-chaperone hypothesis, oxidized lipids,
• MeSH
• alpha-Synuclein MeSH
• Islet Amyloid Polypeptide MeSH
• Amyloid MeSH
• Amyloidogenic Proteins MeSH
• Rats MeSH
• Lipids MeSH
• Intrinsically Disordered Proteins * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Names of Substances
• alpha-Synuclein MeSH
• Islet Amyloid Polypeptide MeSH
• Amyloid MeSH
• Amyloidogenic Proteins MeSH
• Lipids MeSH
• Intrinsically Disordered Proteins * MeSH