Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/56632f12-9a28-4945-81ac-ef46b8543775
- author
- organization
-
- NanoLund: Centre for Nanoscience
- Medical Microspectroscopy (research group)
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- Neuroinflammation (research group)
- Experimental Dementia Research (research group)
- Neural Plasticity and Repair (research group)
- LINXS - Institute of advanced Neutron and X-ray Science
- publishing date
- 2021-03-26
- 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
- 2024-09-21 17:55:12
@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}}, }