A unifying framework for amyloid-mediated membrane damage: The lipid-chaperone hypothesis

0556683 - ÚOCHB 2023 RIV NL eng J - Journal Article
Tempra, Carmelo - Scollo, Federica - Pannuzzo, M. - Lolicato, F. - La Rosa, C.
A unifying framework for amyloid-mediated membrane damage: The lipid-chaperone hypothesis.
Biochimica Et Biophysica Acta-Proteins and Proteomics. Roč. 1870, č. 4 (2022), č. článku 140767. ISSN 1570-9639. E-ISSN 1878-1454
R&D Projects: GA ČR(CZ) GX19-26854X
Institutional support: RVO:61388963 ; RVO:61388955
Keywords : amyloid * aggregation * ion channel-like * model membrane * lipid-chaperone * toxic oligomer
OECD category: Physical chemistry
Impact factor: 3.2, year: 2022
Method of publishing: Limited access
https://doi.org/10.1016/j.bbapap.2022.140767

Over the past thirty years, researchers have highlighted the role played by a class of proteins or polypeptides that forms pathogenic amyloid aggregates in vivo, including i) the amyloid Aβ peptide, which is known to form senile plaques in Alzheimer's disease, ii) α-synuclein, responsible for Lewy body formation in Parkinson's disease and iii) IAPP, which is the protein component of type 2 diabetes-associated islet amyloids. These proteins, known as intrinsically disordered proteins (IDPs), are present as highly dynamic conformational ensembles. IDPs can partially (mis) fold into (dys) functional conformations and accumulate as amyloid aggregates upon interaction with other cytosolic partners such as proteins or lipid membranes. In addition, an increasing number of reports link the toxicity of amyloid proteins to their harmful effects on membrane integrity. Still, the molecular mechanism underlying the amyloidogenic proteins transfer from the aqueous environment to the hydrocarbon core of the membrane is poorly understood. This review starts with a historical overview of the toxicity models of amyloidogenic proteins to contextualize the more recent lipid-chaperone hypothesis. Then, we report the early molecular-level events in the aggregation and ion-channel pore formation of Aβ, IAPP, and α-synuclein interacting with model membranes, emphasizing the complexity of these processes due to their different spatial-temporal resolutions. Next, we underline the need for a combined experimental and computational approach, focusing on the strengths and weaknesses of the most commonly used techniques. Finally, the last two chapters highlight the crucial role of lipid-protein complexes as molecular switches among ion-channel-like formation, detergent-like, and fibril formation mechanisms and their implication in fighting amyloidogenic diseases.
Permanent Link: http://hdl.handle.net/11104/0330806