Authors: | Oliva, Rosario Mukherjee, Sanjib K. Ostermeier, Lena Pazurek, Lilli A. Kriegler, Simon Bader, Verian Prumbaum, Daniel Raunser, Stefan Winklhofer, Konstanze F. Tatzelt, Jörg Winter, Roland |
Title: | Remodeling of the fibrillation pathway of α-synuclein by interaction with antimicrobial peptide LL-III |
Language (ISO): | en |
Abstract: | Liquid-liquid phase separation (LLPS) has emerged as a key mechanism for intracellular organization, and many recent studies have provided important insights into the role of LLPS in cell biology. There is also evidence that LLPS is associated with a variety of medical conditions, including neurodegenerative disorders. Pathological aggregation of α-synuclein, which is causally linked to Parkinson's disease, can proceed via droplet condensation, which then gradually transitions to the amyloid state. We show that the antimicrobial peptide LL-III is able to interact with both monomers and condensates of α-synuclein, leading to stabilization of the droplet and preventing conversion to the fibrillar state. The anti-aggregation activity of LL-III was also confirmed in a cellular model. We anticipate that studying the interaction of antimicrobial-type peptides with liquid condensates such as α-synuclein will contribute to the understanding of disease mechanisms (that arise in such condensates) and may also open up exciting new avenues for intervention. |
Subject Headings: | α-synuclein Antimicrobial peptide Lewy bodies Liquid-liquid phase separation LL-III Protein condensate |
URI: | http://hdl.handle.net/2003/40820 http://dx.doi.org/10.17877/DE290R-22677 |
Issue Date: | 2021-06-24 |
Rights link: | https://creativecommons.org/licenses/by/4.0/ |
Appears in Collections: | Physikalische Chemie |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Chemistry A European J - 2021 - Oliva - Remodeling of the Fibrillation Pathway of ‐Synuclein by Interaction with.pdf | DNB | 3.3 MB | Adobe PDF | View/Open |
This item is protected by original copyright |
This item is licensed under a Creative Commons License