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Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease

Paulus, Agnes LU ; Engdahl, Anders LU ; Yang, Yiyi LU orcid ; Boza Serrano, Antonio LU ; Bachiller, Sara LU ; Torres-Garcia, Laura LU ; Svanbergsson, Alexander LU orcid ; Garcia, Megg LU orcid ; Keppler Gouras, Gunnar LU orcid and Li, Jia-Yi LU , et al. (2021) In International Journal of Molecular Sciences 22(7).
Abstract
Alzheimer’s disease affects millions of lives worldwide. This terminal disease is characterized by the formation of amyloid aggregates, so-called amyloid oligomers. These oligomers are composed of β-sheet structures, which are believed to be neurotoxic. However, the actual secondary structure that contributes most to neurotoxicity remains unknown. This lack of knowledge is due to the challenging nature of characterizing the secondary structure of amyloids in cells. To overcome this and investigate the molecular changes in proteins directly in cells, we used synchrotron-based infrared microspectroscopy, a label-free and non-destructive technique available for in situ molecular imaging, to detect structural changes in proteins and lipids.... (More)
Alzheimer’s disease affects millions of lives worldwide. This terminal disease is characterized by the formation of amyloid aggregates, so-called amyloid oligomers. These oligomers are composed of β-sheet structures, which are believed to be neurotoxic. However, the actual secondary structure that contributes most to neurotoxicity remains unknown. This lack of knowledge is due to the challenging nature of characterizing the secondary structure of amyloids in cells. To overcome this and investigate the molecular changes in proteins directly in cells, we used synchrotron-based infrared microspectroscopy, a label-free and non-destructive technique available for in situ molecular imaging, to detect structural changes in proteins and lipids. Specifically, we evaluated the formation of β-sheet structures in different monogenic and bigenic cellular models of Alzheimer’s disease that we generated for this study. We report on the possibility to discern different amyloid signatures directly in cells using infrared microspectroscopy and demonstrate that bigenic (amyloid-β, α-synuclein) and (amyloid-β, Tau) neuron-like cells display changes in β-sheet load. Altogether, our findings support the notion that different molecular mechanisms of amyloid aggregation, as opposed to a common mechanism, are triggered by the specific cellular environment and, therefore, that various mechanisms lead to the development of Alzheimer’s disease. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
FTIR; amyloid-β; Tau; α-synuclein β-sheet; cellular environment; Alzheimer’s disease
in
International Journal of Molecular Sciences
volume
22
issue
7
article number
3430
publisher
MDPI AG
external identifiers
  • pmid:33810433
  • scopus:85102991660
  • pmid:33810433
ISSN
1422-0067
DOI
10.3390/ijms22073430
language
English
LU publication?
yes
id
56632f12-9a28-4945-81ac-ef46b8543775
date added to LUP
2021-03-29 14:58:05
date last changed
2024-05-04 04:50:25
@article{56632f12-9a28-4945-81ac-ef46b8543775,
  abstract     = {{Alzheimer’s disease affects millions of lives worldwide. This terminal disease is characterized by the formation of amyloid aggregates, so-called amyloid oligomers. These oligomers are composed of β-sheet structures, which are believed to be neurotoxic. However, the actual secondary structure that contributes most to neurotoxicity remains unknown. This lack of knowledge is due to the challenging nature of characterizing the secondary structure of amyloids in cells. To overcome this and investigate the molecular changes in proteins directly in cells, we used synchrotron-based infrared microspectroscopy, a label-free and non-destructive technique available for in situ molecular imaging, to detect structural changes in proteins and lipids. Specifically, we evaluated the formation of β-sheet structures in different monogenic and bigenic cellular models of Alzheimer’s disease that we generated for this study. We report on the possibility to discern different amyloid signatures directly in cells using infrared microspectroscopy and demonstrate that bigenic (amyloid-β, α-synuclein) and (amyloid-β, Tau) neuron-like cells display changes in β-sheet load. Altogether, our findings support the notion that different molecular mechanisms of amyloid aggregation, as opposed to a common mechanism, are triggered by the specific cellular environment and, therefore, that various mechanisms lead to the development of Alzheimer’s disease.}},
  author       = {{Paulus, Agnes and Engdahl, Anders and Yang, Yiyi and Boza Serrano, Antonio and Bachiller, Sara and Torres-Garcia, Laura and Svanbergsson, Alexander and Garcia, Megg and Keppler Gouras, Gunnar and Li, Jia-Yi and Deierborg, Tomas and Klementieva, Oxana}},
  issn         = {{1422-0067}},
  keywords     = {{FTIR; amyloid-β; Tau; α-synuclein β-sheet; cellular environment; Alzheimer’s disease}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{7}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease}},
  url          = {{http://dx.doi.org/10.3390/ijms22073430}},
  doi          = {{10.3390/ijms22073430}},
  volume       = {{22}},
  year         = {{2021}},
}