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2D polarization imaging as a low-cost fluorescence method to detect α-synuclein aggregation ex vivo in models of Parkinson’s disease

Camacho, Rafael; Täuber, Daniela LU ; Hansen, Christian LU ; Shi, Juanzi LU ; Bousset, Luc; Melki, Ronald; Li, Jia-Yi LU and Scheblykin, Ivan LU (2018) In Communications Biology 1.
Abstract
A hallmark of Parkinson’s disease is the formation of large protein-rich aggregates in neurons, where α-synuclein is the most abundant protein. A standard approach to visualize aggregation is to fluorescently label the proteins of interest. Then, highly fluorescent regions are assumed to contain aggregated proteins. However, fluorescence brightness alone cannot discriminate micrometer-sized regions with high expression of non-aggregated proteins from regions where the proteins are aggregated on the molecular scale. Here, we demonstrate that 2-dimensional polarization imaging can discriminate between preformed non-aggregated and aggregated forms of α-synuclein, and detect increased aggregation in brain tissues of transgenic mice. This... (More)
A hallmark of Parkinson’s disease is the formation of large protein-rich aggregates in neurons, where α-synuclein is the most abundant protein. A standard approach to visualize aggregation is to fluorescently label the proteins of interest. Then, highly fluorescent regions are assumed to contain aggregated proteins. However, fluorescence brightness alone cannot discriminate micrometer-sized regions with high expression of non-aggregated proteins from regions where the proteins are aggregated on the molecular scale. Here, we demonstrate that 2-dimensional polarization imaging can discriminate between preformed non-aggregated and aggregated forms of α-synuclein, and detect increased aggregation in brain tissues of transgenic mice. This imaging method assesses homo-FRET between labels by measuring fluorescence polarization in excitation and emission simultaneously, which translates into higher contrast than fluorescence anisotropy imaging. Exploring earlier aggregation states of α-synuclein using such technically simple imaging method could lead to crucial improvements in our understanding of α-synuclein-mediated pathology in Parkinson’s Disease. (Less)
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Contribution to journal
publication status
published
subject
in
Communications Biology
volume
1
publisher
Nature Research
ISSN
2399-3642
DOI
doi.org/10.1038/s42003-018-0156-x
language
English
LU publication?
yes
id
8a23a80d-34b6-476d-950c-69f176de00b5
date added to LUP
2018-10-09 10:54:07
date last changed
2018-11-21 21:42:14
@article{8a23a80d-34b6-476d-950c-69f176de00b5,
  abstract     = {A hallmark of Parkinson’s disease is the formation of large protein-rich aggregates in neurons, where α-synuclein is the most abundant protein. A standard approach to visualize aggregation is to fluorescently label the proteins of interest. Then, highly fluorescent regions are assumed to contain aggregated proteins. However, fluorescence brightness alone cannot discriminate micrometer-sized regions with high expression of non-aggregated proteins from regions where the proteins are aggregated on the molecular scale. Here, we demonstrate that 2-dimensional polarization imaging can discriminate between preformed non-aggregated and aggregated forms of α-synuclein, and detect increased aggregation in brain tissues of transgenic mice. This imaging method assesses homo-FRET between labels by measuring fluorescence polarization in excitation and emission simultaneously, which translates into higher contrast than fluorescence anisotropy imaging. Exploring earlier aggregation states of α-synuclein using such technically simple imaging method could lead to crucial improvements in our understanding of α-synuclein-mediated pathology in Parkinson’s Disease.},
  articleno    = {157 },
  author       = {Camacho, Rafael and Täuber, Daniela and Hansen, Christian and Shi, Juanzi and Bousset, Luc and Melki, Ronald and Li, Jia-Yi and Scheblykin, Ivan},
  issn         = {2399-3642},
  language     = {eng},
  publisher    = {Nature Research},
  series       = {Communications Biology},
  title        = {2D polarization imaging as a low-cost fluorescence method to detect α-synuclein aggregation ex vivo in models of Parkinson’s disease},
  url          = {http://dx.doi.org/doi.org/10.1038/s42003-018-0156-x},
  volume       = {1},
  year         = {2018},
}