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• W4386563908 endingPage "3559" @default.
• W4386563908 startingPage "3551" @default.
• W4386563908 abstract "Abrupt aggregation of misfolded proteins is the underlying molecular cause of numerous pathologies including diabetes type 2 and injection amyloidosis. Although the exact cause of this process is unclear, a growing body of evidence suggests that protein aggregation is linked to a high protein concentration and the presence of lipid membranes. Endosomes are cell organelles that often possess high concentrations of proteins due to their uptake from the extracellular space. However, the role of endosomes in amyloid pathologies remains unclear. In this study, we used a set of biophysical methods to determine the role of bis(monoacylglycero)phosphate (BMP), the major lipid constituent of late endosomes on the aggregation properties of insulin. We found that both saturated and unsaturated BMP accelerated protein aggregation. However, very little if any changes in the secondary structure of insulin fibrils grown in the presence of BMP were observed. Therefore, no changes in the toxicity of these aggregates compared to the fibrils formed in the lipid-free environment were observed. We also found that the toxicity of insulin oligomers formed in the presence of a 77:23 mol/mol ratio of BMP/PC, which represents the lipid composition of late endosomes, was slightly higher than the toxicity of insulin oligomers formed in the lipid-free environment. However, the toxicity of mature insulin fibrils formed in the presence of BMP/PC mixture was found to be lower or similar to the toxicity of insulin fibrils formed in the lipid-free environment. These results suggest that late endosomes are unlikely to be the source of highly toxic protein aggregates if amyloid proteins aggregate in them." @default.
• W4386563908 created "2023-09-10" @default.
• W4386563908 creator A5047543506 @default.
• W4386563908 creator A5061987284 @default.
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• W4386563908 date "2023-09-08" @default.
• W4386563908 modified "2023-10-14" @default.
• W4386563908 title "Elucidation of the Role of Lipids in Late Endosomes on the Aggregation of Insulin" @default.
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• W4386563908 doi "https://doi.org/10.1021/acschemneuro.3c00475" @default.
• W4386563908 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37682720" @default.
• W4386563908 hasPublicationYear "2023" @default.
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