Cargando…
Differential effects of Cu(2+) and Fe(3+) ions on in vitro amyloid formation of biologically-relevant α-synuclein variants
Alterations in metal ion homeostasis appear coupled to neurodegenerative disorders but mechanisms are unknown. Amyloid formation of the protein α-synuclein in brain cells is a hallmark of Parkinson’s disease. α-Synuclein can bind several metal ions in vitro and such interactions may affect the assem...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295844/ https://www.ncbi.nlm.nih.gov/pubmed/32170541 http://dx.doi.org/10.1007/s10534-020-00234-4 |
_version_ | 1783546726457540608 |
---|---|
author | Lorentzon, Emma Kumar, Ranjeet Horvath, Istvan Wittung-Stafshede, Pernilla |
author_facet | Lorentzon, Emma Kumar, Ranjeet Horvath, Istvan Wittung-Stafshede, Pernilla |
author_sort | Lorentzon, Emma |
collection | PubMed |
description | Alterations in metal ion homeostasis appear coupled to neurodegenerative disorders but mechanisms are unknown. Amyloid formation of the protein α-synuclein in brain cells is a hallmark of Parkinson’s disease. α-Synuclein can bind several metal ions in vitro and such interactions may affect the assembly process. Here we used biophysical methods to study the effects of micromolar concentrations of Cu(2+) and Fe(3+) ions on amyloid formation of selected α-synuclein variants (wild-type and A53T α-synuclein, in normal and N-terminally acetylated forms). As shown previously, Cu(2+) speeds up aggregation of normal wild-type α-synuclein, but not the acetylated form. However, Cu(2+) has a minimal effect on (the faster) aggregation of normal A53T α-synuclein, despite that Cu(2+) binds to this variant. Like Cu(2+), Fe(3+) speeds up aggregation of non-acetylated wild-type α-synuclein, but with acetylation, Fe(3+) instead slows down aggregation. In contrast, for A53T α-synuclein, regardless of acetylation, Fe(3+) slows down aggregation with the effect being most dramatic for acetylated A53T α-synuclein. The results presented here suggest a correlation between metal-ion modulation effect and intrinsic aggregation speed of the various α-synuclein variants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10534-020-00234-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7295844 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-72958442020-06-19 Differential effects of Cu(2+) and Fe(3+) ions on in vitro amyloid formation of biologically-relevant α-synuclein variants Lorentzon, Emma Kumar, Ranjeet Horvath, Istvan Wittung-Stafshede, Pernilla Biometals Article Alterations in metal ion homeostasis appear coupled to neurodegenerative disorders but mechanisms are unknown. Amyloid formation of the protein α-synuclein in brain cells is a hallmark of Parkinson’s disease. α-Synuclein can bind several metal ions in vitro and such interactions may affect the assembly process. Here we used biophysical methods to study the effects of micromolar concentrations of Cu(2+) and Fe(3+) ions on amyloid formation of selected α-synuclein variants (wild-type and A53T α-synuclein, in normal and N-terminally acetylated forms). As shown previously, Cu(2+) speeds up aggregation of normal wild-type α-synuclein, but not the acetylated form. However, Cu(2+) has a minimal effect on (the faster) aggregation of normal A53T α-synuclein, despite that Cu(2+) binds to this variant. Like Cu(2+), Fe(3+) speeds up aggregation of non-acetylated wild-type α-synuclein, but with acetylation, Fe(3+) instead slows down aggregation. In contrast, for A53T α-synuclein, regardless of acetylation, Fe(3+) slows down aggregation with the effect being most dramatic for acetylated A53T α-synuclein. The results presented here suggest a correlation between metal-ion modulation effect and intrinsic aggregation speed of the various α-synuclein variants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10534-020-00234-4) contains supplementary material, which is available to authorized users. Springer Netherlands 2020-03-13 2020 /pmc/articles/PMC7295844/ /pubmed/32170541 http://dx.doi.org/10.1007/s10534-020-00234-4 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lorentzon, Emma Kumar, Ranjeet Horvath, Istvan Wittung-Stafshede, Pernilla Differential effects of Cu(2+) and Fe(3+) ions on in vitro amyloid formation of biologically-relevant α-synuclein variants |
title | Differential effects of Cu(2+) and Fe(3+) ions on in vitro amyloid formation of biologically-relevant α-synuclein variants |
title_full | Differential effects of Cu(2+) and Fe(3+) ions on in vitro amyloid formation of biologically-relevant α-synuclein variants |
title_fullStr | Differential effects of Cu(2+) and Fe(3+) ions on in vitro amyloid formation of biologically-relevant α-synuclein variants |
title_full_unstemmed | Differential effects of Cu(2+) and Fe(3+) ions on in vitro amyloid formation of biologically-relevant α-synuclein variants |
title_short | Differential effects of Cu(2+) and Fe(3+) ions on in vitro amyloid formation of biologically-relevant α-synuclein variants |
title_sort | differential effects of cu(2+) and fe(3+) ions on in vitro amyloid formation of biologically-relevant α-synuclein variants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295844/ https://www.ncbi.nlm.nih.gov/pubmed/32170541 http://dx.doi.org/10.1007/s10534-020-00234-4 |
work_keys_str_mv | AT lorentzonemma differentialeffectsofcu2andfe3ionsoninvitroamyloidformationofbiologicallyrelevantasynucleinvariants AT kumarranjeet differentialeffectsofcu2andfe3ionsoninvitroamyloidformationofbiologicallyrelevantasynucleinvariants AT horvathistvan differentialeffectsofcu2andfe3ionsoninvitroamyloidformationofbiologicallyrelevantasynucleinvariants AT wittungstafshedepernilla differentialeffectsofcu2andfe3ionsoninvitroamyloidformationofbiologicallyrelevantasynucleinvariants |