Chemical properties of lipids strongly affect the kinetics of the membrane-induced aggregation of α-synuclein
(2016) In Proceedings of the National Academy of Sciences of the United States of America 113(26). p.7065-7070- Abstract
Intracellular α-synuclein deposits, known as Lewy bodies, have been linked to a range of neurodegenerative disorders, including Parkinson's disease. α-Synuclein binds to synthetic and biological lipids, and this interaction has been shown to play a crucial role for both α-synuclein's native function, including synaptic plasticity, and the initiation of its aggregation. Here, we describe the interplay between the lipid properties and the lipid binding and aggregation propensity of α-synuclein. In particular, we have observed that the binding of α-synuclein to model membranes is much stronger when the latter is in the fluid rather than the gel phase, and that this binding induces a segregation of the lipids into protein-poor and... (More)
Intracellular α-synuclein deposits, known as Lewy bodies, have been linked to a range of neurodegenerative disorders, including Parkinson's disease. α-Synuclein binds to synthetic and biological lipids, and this interaction has been shown to play a crucial role for both α-synuclein's native function, including synaptic plasticity, and the initiation of its aggregation. Here, we describe the interplay between the lipid properties and the lipid binding and aggregation propensity of α-synuclein. In particular, we have observed that the binding of α-synuclein to model membranes is much stronger when the latter is in the fluid rather than the gel phase, and that this binding induces a segregation of the lipids into protein-poor and protein-rich populations. In addition, α-synuclein was found to aggregate at detectable rates only when interacting with membranes composed of the most soluble lipids investigated here. Overall, our results show that the chemical properties of lipids determine whether or not the lipids can trigger the aggregation of α-synuclein, thus affecting the balance between functional and aberrant behavior of the protein.
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- author
- Galvagnion, Céline ; Brown, James W P ; Ouberai, Myriam M. ; Flagmeier, Patrick ; Vendruscolo, Michele ; Buell, Alexander K. ; Sparr, Emma LU and Dobson, Christopher M.
- organization
- publishing date
- 2016-06-28
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Lipid-induced aggregation, Parkinson's disease, Phase diagram, α-synuclein
- in
- Proceedings of the National Academy of Sciences of the United States of America
- volume
- 113
- issue
- 26
- pages
- 6 pages
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:27298346
- wos:000379033400042
- scopus:84976602130
- ISSN
- 0027-8424
- DOI
- 10.1073/pnas.1601899113
- language
- English
- LU publication?
- yes
- id
- 7c73e1f1-f7bd-4244-9fb0-82c34f32feeb
- date added to LUP
- 2017-01-19 13:39:30
- date last changed
- 2025-04-20 03:54:36
@article{7c73e1f1-f7bd-4244-9fb0-82c34f32feeb,
abstract = {{<p>Intracellular α-synuclein deposits, known as Lewy bodies, have been linked to a range of neurodegenerative disorders, including Parkinson's disease. α-Synuclein binds to synthetic and biological lipids, and this interaction has been shown to play a crucial role for both α-synuclein's native function, including synaptic plasticity, and the initiation of its aggregation. Here, we describe the interplay between the lipid properties and the lipid binding and aggregation propensity of α-synuclein. In particular, we have observed that the binding of α-synuclein to model membranes is much stronger when the latter is in the fluid rather than the gel phase, and that this binding induces a segregation of the lipids into protein-poor and protein-rich populations. In addition, α-synuclein was found to aggregate at detectable rates only when interacting with membranes composed of the most soluble lipids investigated here. Overall, our results show that the chemical properties of lipids determine whether or not the lipids can trigger the aggregation of α-synuclein, thus affecting the balance between functional and aberrant behavior of the protein.</p>}},
author = {{Galvagnion, Céline and Brown, James W P and Ouberai, Myriam M. and Flagmeier, Patrick and Vendruscolo, Michele and Buell, Alexander K. and Sparr, Emma and Dobson, Christopher M.}},
issn = {{0027-8424}},
keywords = {{Lipid-induced aggregation; Parkinson's disease; Phase diagram; α-synuclein}},
language = {{eng}},
month = {{06}},
number = {{26}},
pages = {{7065--7070}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences of the United States of America}},
title = {{Chemical properties of lipids strongly affect the kinetics of the membrane-induced aggregation of α-synuclein}},
url = {{http://dx.doi.org/10.1073/pnas.1601899113}},
doi = {{10.1073/pnas.1601899113}},
volume = {{113}},
year = {{2016}},
}