α-Synuclein Aggregation Is Triggered by Oligomeric Amyloid-β 42 via Heterogeneous Primary Nucleation


Date

2023-08-09

Publication Type

Journal Article

ETH Bibliography

yes

Citations

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Data

Abstract

An increasing number of cases where amyloids of different proteins are found in the same patient are being reported. This observation complicates diagnosis and clinical intervention. Amyloids of the amyloid-β peptide or the protein α-synuclein are traditionally considered hallmarks of Alzheimer’s and Parkinson’s diseases, respectively. However, the co-occurrence of amyloids of these proteins has also been reported in patients diagnosed with either disease. Here, we show that soluble species containing amyloid-β can induce the aggregation of α-synuclein. Fibrils formed under these conditions are solely composed of α-synuclein to which amyloid-β can be found associated but not as part of the core of the fibrils. Importantly, by global kinetic analysis, we found that the aggregation of α-synuclein under these conditions occurs via heterogeneous primary nucleation, triggered by soluble aggregates containing amyloid-β.

Publication status

published

Editor

Book title

Volume

145 (33)

Pages / Article No.

18276 - 18285

Publisher

American Chemical Society

Event

Edition / version

Methods

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Geographic location

Date collected

Date created

Subject

Organisational unit

09572 - Arosio, Paolo / Arosio, Paolo check_circle

Notes

Funding

101002094 - Biologically Inspired Molecular Adhesives towards Multifunctional Biomaterials and Microreactors (EC)

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