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Co-Aggregation of S100A9 with DOPA and Cyclen-Based Compounds Manifested in Amyloid Fibril Thickening without Altering Rates of Self-Assembly
Article

The Amyloid Forming Peptides Islet Amyloid Polypeptide and Amyloid β Interact at the Molecular Level

Department of Medical Cell Biology, Uppsala University, 75123 Uppsala, Sweden
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Author to whom correspondence should be addressed.
Academic Editor: Ludmilla A. Morozova-Roche
Int. J. Mol. Sci. 2021, 22(20), 11153; https://doi.org/10.3390/ijms222011153
Received: 13 September 2021 / Revised: 9 October 2021 / Accepted: 12 October 2021 / Published: 15 October 2021
(This article belongs to the Special Issue Amyloid Hetero-Aggregation)
Epidemiological studies support a connection between the two common disorders, type-2 diabetes and Alzheimer’s disease. Both conditions have local amyloid formation in their pathogenesis, and cross-seeding between islet amyloid polypeptide (IAPP) and amyloid β (Aβ) could constitute the link. The bimolecular fluorescence complementation (BiFC) assay was used to investigate the occurrence of heterologous interactions between IAPP and Aβ and to compare the potential toxic effects of IAPP/Aβ, IAPP/IAPP, and Aβ/Aβ expression in living cells. Microscopy was used to confirm the fluorescence and determine the lysosomal, mitochondrial areas and mitochondrial membrane potential, and a FACS analysis was used to determine ROS production and the role for autophagy. Drosophila melanogaster expressing IAPP and Aβ was used to study their co-deposition and effects on longevity. We showed that the co-expression of IAPP and Aβ resulted in fluorophore reconstitution to the same extent as determined for homologous IAPP/IAPP or Aβ/Aβ expression. The BiFC(+)/BiFC(−) ratio of lysosomal area calculations increased in transfected cells independent of the vector combinations, while only Aβ/Aβ expression increased mitochondrial membrane potential. Expression combinations containing Aβ were necessary for the formation of a congophilic amyloid. In Drosophila melanogaster expressing IAPP/Aβ, co-deposition of the amyloid-forming peptides caused reduced longevity. The BiFC results confirmed a heterologous interaction between IAPP and Aβ, while co-deposits in the brain of Drosophila suggest mixed amyloid aggregates. View Full-Text
Keywords: Aβ; BiFC; cross-seeding Drosophila melanogaster; IAPP ; BiFC; cross-seeding Drosophila melanogaster; IAPP
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MDPI and ACS Style

Wang, Y.; Westermark, G.T. The Amyloid Forming Peptides Islet Amyloid Polypeptide and Amyloid β Interact at the Molecular Level. Int. J. Mol. Sci. 2021, 22, 11153. https://doi.org/10.3390/ijms222011153

AMA Style

Wang Y, Westermark GT. The Amyloid Forming Peptides Islet Amyloid Polypeptide and Amyloid β Interact at the Molecular Level. International Journal of Molecular Sciences. 2021; 22(20):11153. https://doi.org/10.3390/ijms222011153

Chicago/Turabian Style

Wang, Ye, and Gunilla T. Westermark. 2021. "The Amyloid Forming Peptides Islet Amyloid Polypeptide and Amyloid β Interact at the Molecular Level" International Journal of Molecular Sciences 22, no. 20: 11153. https://doi.org/10.3390/ijms222011153

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