Related Experiment Video
Updated: Jul 9, 2025
06:17
A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
Published on: May 22, 2018
11.9K
Ganglioside Micelles Affect Amyloid β Aggregation by Coassembly.
Jing Hu1, Sara Linse2, Emma Sparr1
1Division of Physical Chemistry, Lund University, SE-22100 Lund, Sweden.
ACS Chemical Neuroscience
|December 5, 2023
Summary
Gangliosides like GM1 interact with amyloid beta (Aβ) peptides, influencing Alzheimer's disease plaque formation. GM1 affects Aβ40 and Aβ42 aggregation differently, potentially inhibiting fibril growth.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Alzheimer's disease (AD) is characterized by extracellular amyloid plaques primarily composed of amyloid beta (Aβ) peptides.
- Gangliosides, abundant neuronal lipids, are also found in AD plaques and can form mixed micelles with Aβ.
- Understanding lipid-peptide interactions is crucial for elucidating AD pathogenesis.
Purpose of the Study:
- To investigate the coassembly of ganglioside GM1 with Aβ40 and Aβ42 peptides.
- To examine the impact of GM1 on the aggregation kinetics and mechanisms of Aβ40 and Aβ42.
- To explore the role of glycolipid-peptide interactions in Alzheimer's disease pathology.
Main Methods:
- Microfluidic diffusional sizing
- Confocal microscopy
- Cryogenic transmission electron microscopy (cryo-TEM)
- Fluorescence spectroscopy
Main Results:
- GM1 coassembles with both Aβ monomers and Aβ fibrils.
- Non-seeded Aβ40 aggregation is delayed by GM1, while Aβ42 aggregation is accelerated.
- GM1 addition retards seeded aggregation for both Aβ40 and Aβ42, suggesting inhibition of fibril elongation.
- Differential effects on nucleation but potential common inhibition of elongation were observed.
Conclusions:
- GM1 significantly influences Aβ aggregation pathways, with distinct effects on nucleation for Aβ40 and Aβ42.
- GM1 may act as an inhibitor of amyloid fibril elongation for both Aβ40 and Aβ42.
- These findings highlight the critical role of ganglioside-lipid interactions in Alzheimer's disease pathogenesis.
Related Concept Videos
03:03Amyloid Fibrils
9.6K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
9.6K
01:24Oligosaccharide Assembly
2.9K
Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
Multiple sugar molecules that may or may...
2.9K