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Stabilization of α-synuclein oligomers using formaldehyde
by
Reimer, Lasse
, Jensen, Poul Henning
, Gregersen, Emil
, Betzer, Cristine
, Ruesink, Harm
, Moeller, Arne
in
alpha-Synuclein - chemistry
/ alpha-Synuclein - metabolism
/ Amyloid
/ Amyloid - chemistry
/ Amyloid - metabolism
/ Antibodies
/ Antigenicity
/ Atrophy
/ Biology and Life Sciences
/ Biomarkers
/ Brain
/ Brain research
/ Conformation
/ Crosslinking
/ Dementia disorders
/ Enzyme-linked immunosorbent assay
/ Formaldehyde
/ Formaldehyde - chemistry
/ Humans
/ Inclusions
/ Incubation
/ Intermediates
/ Lewy bodies
/ Lewy Body Disease - metabolism
/ Medicine and Health Sciences
/ Methods
/ Microscopy
/ Movement disorders
/ Multiple System Atrophy - metabolism
/ Neurodegenerative diseases
/ Neurosciences
/ Oligomers
/ Parkinson Disease - metabolism
/ Parkinson's disease
/ Physical Sciences
/ Protein Multimerization
/ Protein Stability
/ Proteins
/ Research and Analysis Methods
/ Synuclein
/ Urea
/ Ureas
2019
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Stabilization of α-synuclein oligomers using formaldehyde
by
Reimer, Lasse
, Jensen, Poul Henning
, Gregersen, Emil
, Betzer, Cristine
, Ruesink, Harm
, Moeller, Arne
in
alpha-Synuclein - chemistry
/ alpha-Synuclein - metabolism
/ Amyloid
/ Amyloid - chemistry
/ Amyloid - metabolism
/ Antibodies
/ Antigenicity
/ Atrophy
/ Biology and Life Sciences
/ Biomarkers
/ Brain
/ Brain research
/ Conformation
/ Crosslinking
/ Dementia disorders
/ Enzyme-linked immunosorbent assay
/ Formaldehyde
/ Formaldehyde - chemistry
/ Humans
/ Inclusions
/ Incubation
/ Intermediates
/ Lewy bodies
/ Lewy Body Disease - metabolism
/ Medicine and Health Sciences
/ Methods
/ Microscopy
/ Movement disorders
/ Multiple System Atrophy - metabolism
/ Neurodegenerative diseases
/ Neurosciences
/ Oligomers
/ Parkinson Disease - metabolism
/ Parkinson's disease
/ Physical Sciences
/ Protein Multimerization
/ Protein Stability
/ Proteins
/ Research and Analysis Methods
/ Synuclein
/ Urea
/ Ureas
2019
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Stabilization of α-synuclein oligomers using formaldehyde
by
Reimer, Lasse
, Jensen, Poul Henning
, Gregersen, Emil
, Betzer, Cristine
, Ruesink, Harm
, Moeller, Arne
in
alpha-Synuclein - chemistry
/ alpha-Synuclein - metabolism
/ Amyloid
/ Amyloid - chemistry
/ Amyloid - metabolism
/ Antibodies
/ Antigenicity
/ Atrophy
/ Biology and Life Sciences
/ Biomarkers
/ Brain
/ Brain research
/ Conformation
/ Crosslinking
/ Dementia disorders
/ Enzyme-linked immunosorbent assay
/ Formaldehyde
/ Formaldehyde - chemistry
/ Humans
/ Inclusions
/ Incubation
/ Intermediates
/ Lewy bodies
/ Lewy Body Disease - metabolism
/ Medicine and Health Sciences
/ Methods
/ Microscopy
/ Movement disorders
/ Multiple System Atrophy - metabolism
/ Neurodegenerative diseases
/ Neurosciences
/ Oligomers
/ Parkinson Disease - metabolism
/ Parkinson's disease
/ Physical Sciences
/ Protein Multimerization
/ Protein Stability
/ Proteins
/ Research and Analysis Methods
/ Synuclein
/ Urea
/ Ureas
2019
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Journal Article
Stabilization of α-synuclein oligomers using formaldehyde
2019
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Overview
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ alpha-Synuclein - metabolism
/ Amyloid
/ Atrophy
/ Brain
/ Enzyme-linked immunosorbent assay
/ Humans
/ Lewy Body Disease - metabolism
/ Medicine and Health Sciences
/ Methods
/ Multiple System Atrophy - metabolism
/ Parkinson Disease - metabolism
/ Proteins
/ Research and Analysis Methods
/ Urea
/ Ureas
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