TY  - JOUR
A1  - Ruesink, Harm
A1  - Reimer, Lasse
A1  - Gregersen, Emil
A1  - Möller, Arne
A1  - Betzer, Cristine
A1  - Jensen, Poul Henning
T1  - Stabilization of α-synuclein oligomers using formaldehyde
T2  - PLoS one
N2  - 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.
KW  - Oligomers
KW  - Monomers
KW  - Enzyme-linked immunoassays
KW  - Cross-linking
KW  - Formaldehyde
KW  - Amyloid proteins
KW  - Antigens
KW  - Parkinson disease
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51087
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-510875
SN  - 1932-6203
N1  - 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.
VL  - 14
IS  - (10): e0216764
SP  - 1
EP  - 11
PB  - PLoS
CY  - Lawrence, Kan.
ER  -