Strong inhibition of peptide amyloid formation by a fatty acid
(2021) In Biophysical Journal 120(20). p.4536-4546- Abstract
The aggregation of peptides into amyloid fibrils is associated with several diseases, including Alzheimer's and Parkinson's disease. Because hydrophobic interactions often play an important role in amyloid formation, the presence of various hydrophobic or amphiphilic molecules, such as lipids, may influence the aggregation process. We have studied the effect of a fatty acid, linoleic acid, on the fibrillation process of the amyloid-forming model peptide NACore (GAVVTGVTAVA). NACore is a peptide fragment spanning residue 68–78 of the protein α-synuclein involved in Parkinson's disease. Based primarily on circular dichroism measurements, we found that even a very small amount of linoleic acid can substantially inhibit the fibrillation of... (More)
The aggregation of peptides into amyloid fibrils is associated with several diseases, including Alzheimer's and Parkinson's disease. Because hydrophobic interactions often play an important role in amyloid formation, the presence of various hydrophobic or amphiphilic molecules, such as lipids, may influence the aggregation process. We have studied the effect of a fatty acid, linoleic acid, on the fibrillation process of the amyloid-forming model peptide NACore (GAVVTGVTAVA). NACore is a peptide fragment spanning residue 68–78 of the protein α-synuclein involved in Parkinson's disease. Based primarily on circular dichroism measurements, we found that even a very small amount of linoleic acid can substantially inhibit the fibrillation of NACore. This inhibitory effect manifests itself through a prolongation of the lag phase of the peptide fibrillation. The effect is greatest when the fatty acid is present from the beginning of the process together with the monomeric peptide. Cryogenic transmission electron microscopy revealed the presence of nonfibrillar clusters among NACore fibrils formed in the presence of linoleic acid. We argue that the observed inhibitory effect on fibrillation is due to co-association of peptide oligomers and fatty acid aggregates at the early stage of the process. An important aspect of this mechanism is that it is nonmonomeric peptide structures that associate with the fatty acid aggregates. Similar mechanisms of action could be relevant in amyloid formation occurring in vivo, where the aggregation takes place in a lipid-rich environment.
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- author
- Pallbo, Jon LU ; Olsson, Ulf LU and Sparr, Emma LU
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biophysical Journal
- volume
- 120
- issue
- 20
- pages
- 4536 - 4546
- publisher
- Cell Press
- external identifiers
-
- scopus:85114687295
- pmid:34478699
- ISSN
- 0006-3495
- DOI
- 10.1016/j.bpj.2021.08.035
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2021 Biophysical Society
- id
- 4d08c0ce-38a5-4606-9c94-4856ee021c73
- date added to LUP
- 2021-10-13 14:07:12
- date last changed
- 2024-06-15 18:08:52
@article{4d08c0ce-38a5-4606-9c94-4856ee021c73,
abstract = {{<p>The aggregation of peptides into amyloid fibrils is associated with several diseases, including Alzheimer's and Parkinson's disease. Because hydrophobic interactions often play an important role in amyloid formation, the presence of various hydrophobic or amphiphilic molecules, such as lipids, may influence the aggregation process. We have studied the effect of a fatty acid, linoleic acid, on the fibrillation process of the amyloid-forming model peptide NACore (GAVVTGVTAVA). NACore is a peptide fragment spanning residue 68–78 of the protein α-synuclein involved in Parkinson's disease. Based primarily on circular dichroism measurements, we found that even a very small amount of linoleic acid can substantially inhibit the fibrillation of NACore. This inhibitory effect manifests itself through a prolongation of the lag phase of the peptide fibrillation. The effect is greatest when the fatty acid is present from the beginning of the process together with the monomeric peptide. Cryogenic transmission electron microscopy revealed the presence of nonfibrillar clusters among NACore fibrils formed in the presence of linoleic acid. We argue that the observed inhibitory effect on fibrillation is due to co-association of peptide oligomers and fatty acid aggregates at the early stage of the process. An important aspect of this mechanism is that it is nonmonomeric peptide structures that associate with the fatty acid aggregates. Similar mechanisms of action could be relevant in amyloid formation occurring in vivo, where the aggregation takes place in a lipid-rich environment.</p>}},
author = {{Pallbo, Jon and Olsson, Ulf and Sparr, Emma}},
issn = {{0006-3495}},
language = {{eng}},
number = {{20}},
pages = {{4536--4546}},
publisher = {{Cell Press}},
series = {{Biophysical Journal}},
title = {{Strong inhibition of peptide amyloid formation by a fatty acid}},
url = {{http://dx.doi.org/10.1016/j.bpj.2021.08.035}},
doi = {{10.1016/j.bpj.2021.08.035}},
volume = {{120}},
year = {{2021}},
}