Ganglioside Micelles Affect Amyloid β Aggregation by Coassembly
(2023) In ACS Chemical Neuroscience 14(24). p.4335-4343- Abstract
Amyloid β peptide (Aβ) is the crucial protein component of extracellular plaques in Alzheimer’s disease. The plaques also contain gangliosides lipids, which are abundant in membranes of neuronal cells and in cell-derived vesicles and exosomes. When present at concentrations above its critical micelle concentration (cmc), gangliosides can occur as mixed micelles. Here, we study the coassembly of the ganglioside GM1 and the Aβ peptides Aβ40 and 42 by means of microfluidic diffusional sizing, confocal microscopy, and cryogenic transmission electron microscopy. We also study the effects of lipid-peptide interactions on the amyloid aggregation process by fluorescence spectroscopy. Our results reveal coassembly of GM1 lipids with both Aβ... (More)
Amyloid β peptide (Aβ) is the crucial protein component of extracellular plaques in Alzheimer’s disease. The plaques also contain gangliosides lipids, which are abundant in membranes of neuronal cells and in cell-derived vesicles and exosomes. When present at concentrations above its critical micelle concentration (cmc), gangliosides can occur as mixed micelles. Here, we study the coassembly of the ganglioside GM1 and the Aβ peptides Aβ40 and 42 by means of microfluidic diffusional sizing, confocal microscopy, and cryogenic transmission electron microscopy. We also study the effects of lipid-peptide interactions on the amyloid aggregation process by fluorescence spectroscopy. Our results reveal coassembly of GM1 lipids with both Aβ monomers and Aβ fibrils. The results of the nonseeded kinetics experiments show that Aβ40 aggregation is delayed with increasing GM1 concentration, while that of Aβ42 is accelerated. In seeded aggregation reactions, the addition of GM1 leads to a retardation of the aggregation process of both peptides. Thus, while the effect on nucleation differs between the two peptides, GM1 may inhibit the elongation of both types of fibrils. These results shed light on glycolipid-peptide interactions that may play an important role in Alzheimer’s pathology.
(Less)
- author
- Hu, Jing LU ; Linse, Sara LU and Sparr, Emma LU
- organization
- publishing date
- 2023-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- amyloid β, coassembly, GM1 micelle, kinetics, microfluidic diffusional sizing, microscopy
- in
- ACS Chemical Neuroscience
- volume
- 14
- issue
- 24
- pages
- 9 pages
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- pmid:38050745
- scopus:85180087898
- ISSN
- 1948-7193
- DOI
- 10.1021/acschemneuro.3c00524
- language
- English
- LU publication?
- yes
- id
- 19ab7e58-9bfa-4bbb-8649-3e399bc76c22
- date added to LUP
- 2024-01-09 15:13:00
- date last changed
- 2024-04-24 11:09:07
@article{19ab7e58-9bfa-4bbb-8649-3e399bc76c22,
abstract = {{<p>Amyloid β peptide (Aβ) is the crucial protein component of extracellular plaques in Alzheimer’s disease. The plaques also contain gangliosides lipids, which are abundant in membranes of neuronal cells and in cell-derived vesicles and exosomes. When present at concentrations above its critical micelle concentration (cmc), gangliosides can occur as mixed micelles. Here, we study the coassembly of the ganglioside GM1 and the Aβ peptides Aβ40 and 42 by means of microfluidic diffusional sizing, confocal microscopy, and cryogenic transmission electron microscopy. We also study the effects of lipid-peptide interactions on the amyloid aggregation process by fluorescence spectroscopy. Our results reveal coassembly of GM1 lipids with both Aβ monomers and Aβ fibrils. The results of the nonseeded kinetics experiments show that Aβ40 aggregation is delayed with increasing GM1 concentration, while that of Aβ42 is accelerated. In seeded aggregation reactions, the addition of GM1 leads to a retardation of the aggregation process of both peptides. Thus, while the effect on nucleation differs between the two peptides, GM1 may inhibit the elongation of both types of fibrils. These results shed light on glycolipid-peptide interactions that may play an important role in Alzheimer’s pathology.</p>}},
author = {{Hu, Jing and Linse, Sara and Sparr, Emma}},
issn = {{1948-7193}},
keywords = {{amyloid β; coassembly; GM1 micelle; kinetics; microfluidic diffusional sizing; microscopy}},
language = {{eng}},
number = {{24}},
pages = {{4335--4343}},
publisher = {{The American Chemical Society (ACS)}},
series = {{ACS Chemical Neuroscience}},
title = {{Ganglioside Micelles Affect Amyloid β Aggregation by Coassembly}},
url = {{http://dx.doi.org/10.1021/acschemneuro.3c00524}},
doi = {{10.1021/acschemneuro.3c00524}},
volume = {{14}},
year = {{2023}},
}