Strikingly different effects of cholesterol and 7-ketocholesterol on lipid bilayer-mediated aggregation of amyloid beta (1-42)
| Autor: | Mun'delanji C. Vestergaard, Naofumi Shimokawa, Masahiro Takagi, Huong T.T. Phan, Neha Sharma |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Amyloid beta Amyloid beta aggregation Kinetics Biophysics Peptide Lipid vesicles Fibril Biochemistry Pathogenesis lcsh:Biochemistry 03 medical and health sciences chemistry.chemical_compound lcsh:QD415-436 Lipid bilayer Cytotoxicity lcsh:QH301-705.5 7-ketocholesterol chemistry.chemical_classification Membranes biology Cholesterol 030104 developmental biology chemistry lcsh:Biology (General) biology.protein Research Article |
| Zdroj: | Biochemistry and Biophysics Reports, Vol 14, Iss C, Pp 98-103 (2018) Biochemistry and Biophysics Reports |
| ISSN: | 2405-5808 |
| Popis: | Oxidized cholesterol has been widely reported to contribute to the pathogenesis of Alzheimer's disease (AD). However, the mechanism by which they affect the disease is not fully understood. Herein, we aimed to investigate the effect of 7-ketocholesterol (7keto) on membrane-mediated aggregation of amyloid beta (Aβ-42), one of the critical pathogenic events in AD. We have shown that when cholesterol is present in lipid vesicles, kinetics of Aβ nuclei formation is moderately hindered while that of fibril growth was considerably accelerated. The partial substitution of cholesterol with 7keto slightly enhanced the formation of Aβ-42 nuclei and remarkably decreased fibril elongation, thus maintaining the peptide in protofibrillar aggregates, which are reportedly the most toxic species. These findings add in understanding of how cholesterol and its oxidation can affect Aβ-induced cytotoxicity. Highlights • Cholesterol and 7-ketocholesterol membranes had different effects on Aβ aggregation. • Cholesterol-containing membranes considerably accelerated fibril elongation of Aβ-42. • 7-ketocholesterol membranes remarkably decreased Aβ-42 fibril elongation. |
| Databáze: | OpenAIRE |
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