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Misfolding of Amyloidogenic Proteins and Their Interactions with Membranes
Department of Physics, University of Genoa, Genoa 16146, Italy
Research Centre on the Molecular Basis of Neurodegeneration, Florence 50134 Italy
Department of Chemistry, Saint Lawrence University, Canton, NY 13617, USA
All authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 4 November 2013; in revised form: 13 December 2013 / Accepted: 17 December 2013 / Published: 27 December 2013
Abstract: In this paper, we discuss amyloidogenic proteins, their misfolding, resulting structures, and interactions with membranes, which lead to membrane damage and subsequent cell death. Many of these proteins are implicated in serious illnesses such as Alzheimer’s disease and Parkinson’s disease. Misfolding of amyloidogenic proteins leads to the formation of polymorphic oligomers and fibrils. Oligomeric aggregates are widely thought to be the toxic species, however, fibrils also play a role in membrane damage. We focus on the structure of these aggregates and their interactions with model membranes. Study of interactions of amlyoidogenic proteins with model and natural membranes has shown the importance of the lipid bilayer in protein misfolding and aggregation and has led to the development of several models for membrane permeabilization by the resulting amyloid aggregates. We discuss several of these models: formation of structured pores by misfolded amyloidogenic proteins, extraction of lipids, interactions with receptors in biological membranes, and membrane destabilization by amyloid aggregates perhaps analogous to that caused by antimicrobial peptides.
Keywords: amyloidogenic proteins; misfolding; amyloid aggregation; fibrillogenesis; membrane permeabilization; amyloid toxicity
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MDPI and ACS Style
Relini, A.; Marano, N.; Gliozzi, A. Misfolding of Amyloidogenic Proteins and Their Interactions with Membranes. Biomolecules 2014, 4, 20-55.
Relini A, Marano N, Gliozzi A. Misfolding of Amyloidogenic Proteins and Their Interactions with Membranes. Biomolecules. 2014; 4(1):20-55.
Relini, Annalisa; Marano, Nadia; Gliozzi, Alessandra. 2014. "Misfolding of Amyloidogenic Proteins and Their Interactions with Membranes." Biomolecules 4, no. 1: 20-55.