Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease
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 c...
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doaj-051a3508e4684a84803f172d1508221b2021-03-27T00:05:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-03-01223430343010.3390/ijms22073430Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s DiseaseAgnes Paulus0Anders Engdahl1Yiyi Yang2Antonio Boza-Serrano3Sara Bachiller4Laura Torres-Garcia5Alexander Svanbergsson6Megg G. Garcia7Gunnar K. Gouras8Jia-Yi Li9Tomas Deierborg10Oxana Klementieva11Medical Microspectroscopy Laboratory, Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenMedical Microspectroscopy Laboratory, Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenExperimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenExperimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenExperimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenExperimental Dementia Research Unit, Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenNeural Plasticity and Repair Unit, Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenExperimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenExperimental Dementia Research Unit, Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenNeural Plasticity and Repair Unit, Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenExperimental Neuroinflammation Laboratory, Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenMedical Microspectroscopy Laboratory, Department of Experimental Medical Science, Lund University, 22184 Lund, SwedenAlzheimer’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.https://www.mdpi.com/1422-0067/22/7/3430FTIRamyloid-βTauα-synuclein β-sheetcellular environmentAlzheimer’s disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Agnes Paulus Anders Engdahl Yiyi Yang Antonio Boza-Serrano Sara Bachiller Laura Torres-Garcia Alexander Svanbergsson Megg G. Garcia Gunnar K. Gouras Jia-Yi Li Tomas Deierborg Oxana Klementieva |
spellingShingle |
Agnes Paulus Anders Engdahl Yiyi Yang Antonio Boza-Serrano Sara Bachiller Laura Torres-Garcia Alexander Svanbergsson Megg G. Garcia Gunnar K. Gouras Jia-Yi Li Tomas Deierborg Oxana Klementieva Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease International Journal of Molecular Sciences FTIR amyloid-β Tau α-synuclein β-sheet cellular environment Alzheimer’s disease |
author_facet |
Agnes Paulus Anders Engdahl Yiyi Yang Antonio Boza-Serrano Sara Bachiller Laura Torres-Garcia Alexander Svanbergsson Megg G. Garcia Gunnar K. Gouras Jia-Yi Li Tomas Deierborg Oxana Klementieva |
author_sort |
Agnes Paulus |
title |
Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease |
title_short |
Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease |
title_full |
Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease |
title_fullStr |
Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease |
title_full_unstemmed |
Amyloid Structural Changes Studied by Infrared Microspectroscopy in Bigenic Cellular Models of Alzheimer’s Disease |
title_sort |
amyloid structural changes studied by infrared microspectroscopy in bigenic cellular models of alzheimer’s disease |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-03-01 |
description |
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. |
topic |
FTIR amyloid-β Tau α-synuclein β-sheet cellular environment Alzheimer’s disease |
url |
https://www.mdpi.com/1422-0067/22/7/3430 |
work_keys_str_mv |
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