Proteomics

Dataset Information

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GM1 promotes early Aβ oligomer formation and maintenance


ABSTRACT: The aggregation of amyloid beta (Aβ) peptide is associated with Alzheimer’s disease (AD) pathogenesis. Cell membrane composition, especially monosialotetrahexosylganglioside (GM1), is known to promote the formation of Aβ fibrils, yet little is known about the roles of GM1 in the early steps of Aβ oligomer formation. Here, by using GM1-contained liposomes as a mimic of neuronal cell membrane, we demonstrate that GM1 is a critical trigger of Aβ oligomerization and aggregation. We find that GM1 not only promotes the formation of Aβ fibrils, but also facilitates the maintenance of Aβ oligomers on liposome membranes. We structurally characterize the Aβ oligomers formed on the membrane and find that GM1 captures Aβ by binding to its arginine-5 residue. To interrogate the mechanism of Aβ oligomer toxicity, we design a new liposome-based Ca2+-encapsulation assay and provide new evidence for the Aβ ion channel hypothesis. Finally, we conduct cell viability assay to determine the toxicity of Aβ oligomers formed on membranes. Overall, by uncovering the roles of GM1 in mediating early Aβ oligomer formation and maintenance, our work provides a novel direction for pharmaceutical research for AD.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Nikolay Dokholyan  

LAB HEAD: Nikolay V. Dokholyan

PROVIDER: PXD029117 | Pride | 2023-05-10

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
liposome_fibrils.mgf Mgf
liposome_fibrils.xlsx Xlsx
liposome_oligomers..zip Other
liposome_oligomers.mgf Mgf
liposome_oligomers.xlsx Xlsx
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Publications

Monosialotetrahexosylganglioside Promotes Early Aβ42 Oligomer Formation and Maintenance.

Zhang Dong Yan DY   Wang Jian J   Fleeman Rebecca M RM   Kuhn Madison K MK   Swulius Matthew T MT   Proctor Elizabeth A EA   Dokholyan Nikolay V NV  

ACS chemical neuroscience 20220617 13


The aggregation of the amyloid beta (Aβ) peptide is associated with Alzheimer's disease (AD) pathogenesis. Cell membrane composition, especially monosialotetrahexosylganglioside (GM1), is known to promote the formation of Aβ fibrils, yet little is known about the roles of GM1 in the early steps of Aβ oligomer formation. Here, by using GM1-contained liposomes as a mimic of the neuronal cell membrane, we demonstrate that GM1 is a critical trigger of Aβ oligomerization and aggregation. We find that  ...[more]

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