Stabilization of α-synuclein oligomers using formaldehyde
- The group of neurodegenerative diseases, Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) all exhibit inclusions containing amyloid-type α-synuclein (α-syn) aggregates within degenerating brain cells. α-syn also exists as soluble oligomeric species that are hypothesized to represent intermediates between its native and aggregated states. These oligomers are present in brain extracts from patients suffering from synucleinopathies and hold great potential as biomarkers. Although easily prepared in vitro, oligomers are metastable and dissociate over time, thereby complicating α-syn oligomer research. Using the small amine-reactive cross-linker, formaldehyde (FA), we successfully stabilized α-syn oligomers without affecting their size, overall structure or antigenicity towards aggregate-conformation specific α-syn antibodies FILA and MJFR-14-6-4-2. Further, cross-linked α-syn oligomers show resistance towards denaturant like urea and SDS treatment and remain fully functional as internal standard in an aggregation-specific enzyme-linked immunosorbent assay (ELISA) despite prior incubation with urea. We propose that FA cross-linked α-syn oligomers could serve as important calibrators to facilitate comparative and standardized α-syn biomarker studies going forward.
Author: | Harm Ruesink, Lasse Reimer, Emil Gregersen, Arne Möller, Cristine Betzer, Poul Henning Jensen |
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URN: | urn:nbn:de:hebis:30:3-510875 |
DOI: | https://doi.org/10.1371/journal.pone.0216764 |
ISSN: | 1932-6203 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31603909 |
Parent Title (English): | PLoS one |
Publisher: | PLoS |
Place of publication: | Lawrence, Kan. |
Contributor(s): | Mark R. Cookson |
Document Type: | Article |
Language: | English |
Year of Completion: | 2019 |
Date of first Publication: | 2019/10/11 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2019/10/14 |
Tag: | Amyloid proteins; Antigens; Cross-linking; Enzyme-linked immunoassays; Formaldehyde; Monomers; Oligomers; Parkinson disease |
Volume: | 14 |
Issue: | (10): e0216764 |
Page Number: | 11 |
First Page: | 1 |
Last Page: | 11 |
Note: | Copyright: © 2019 Ruesink et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
HeBIS-PPN: | 455389144 |
Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 4.0 |