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The Aβ42 Peptide and IAPP Physically Interact in a Yeast-Based Assay
Numerous studies have demonstrated that people with type 2 diabetes mellitus (associated with IAPP peptide aggregation) show an increased incidence of Alzheimer’s disease (associated with Aβ aggregation), but the mechanism responsible for this correlation is presently unknown. Here, we applied a yea...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531723/ https://www.ncbi.nlm.nih.gov/pubmed/37762425 http://dx.doi.org/10.3390/ijms241814122 |
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author | Kachkin, Daniel V. Lashkul, Veronika V. Gorsheneva, Natalia A. Fedotov, Sergey A. Rubel, Maria S. Chernoff, Yury O. Rubel, Aleksandr A. |
author_facet | Kachkin, Daniel V. Lashkul, Veronika V. Gorsheneva, Natalia A. Fedotov, Sergey A. Rubel, Maria S. Chernoff, Yury O. Rubel, Aleksandr A. |
author_sort | Kachkin, Daniel V. |
collection | PubMed |
description | Numerous studies have demonstrated that people with type 2 diabetes mellitus (associated with IAPP peptide aggregation) show an increased incidence of Alzheimer’s disease (associated with Aβ aggregation), but the mechanism responsible for this correlation is presently unknown. Here, we applied a yeast-based model to study the interactions of IAPP with PrP (associated with TSEs) and with the Aβ42 peptide. We demonstrated that fluorescently tagged IAPP forms detergent-resistant aggregates in yeast cells. Using the FRET approach, we showed that IAPP and Aβ aggregates co-localize and physically interact in yeast cells. We also showed that this interaction is specific and that there is no interaction between IAPP and PrP in the yeast system. Our data confirmed a direct physical interaction between IAPP and Aβ42 aggregates in a living cell. Based on these findings, we hypothesize that this interaction may play a crucial role in seeding Aβ42 aggregation in T2DM patients, thereby promoting the development of AD. |
format | Online Article Text |
id | pubmed-10531723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105317232023-09-28 The Aβ42 Peptide and IAPP Physically Interact in a Yeast-Based Assay Kachkin, Daniel V. Lashkul, Veronika V. Gorsheneva, Natalia A. Fedotov, Sergey A. Rubel, Maria S. Chernoff, Yury O. Rubel, Aleksandr A. Int J Mol Sci Article Numerous studies have demonstrated that people with type 2 diabetes mellitus (associated with IAPP peptide aggregation) show an increased incidence of Alzheimer’s disease (associated with Aβ aggregation), but the mechanism responsible for this correlation is presently unknown. Here, we applied a yeast-based model to study the interactions of IAPP with PrP (associated with TSEs) and with the Aβ42 peptide. We demonstrated that fluorescently tagged IAPP forms detergent-resistant aggregates in yeast cells. Using the FRET approach, we showed that IAPP and Aβ aggregates co-localize and physically interact in yeast cells. We also showed that this interaction is specific and that there is no interaction between IAPP and PrP in the yeast system. Our data confirmed a direct physical interaction between IAPP and Aβ42 aggregates in a living cell. Based on these findings, we hypothesize that this interaction may play a crucial role in seeding Aβ42 aggregation in T2DM patients, thereby promoting the development of AD. MDPI 2023-09-15 /pmc/articles/PMC10531723/ /pubmed/37762425 http://dx.doi.org/10.3390/ijms241814122 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kachkin, Daniel V. Lashkul, Veronika V. Gorsheneva, Natalia A. Fedotov, Sergey A. Rubel, Maria S. Chernoff, Yury O. Rubel, Aleksandr A. The Aβ42 Peptide and IAPP Physically Interact in a Yeast-Based Assay |
title | The Aβ42 Peptide and IAPP Physically Interact in a Yeast-Based Assay |
title_full | The Aβ42 Peptide and IAPP Physically Interact in a Yeast-Based Assay |
title_fullStr | The Aβ42 Peptide and IAPP Physically Interact in a Yeast-Based Assay |
title_full_unstemmed | The Aβ42 Peptide and IAPP Physically Interact in a Yeast-Based Assay |
title_short | The Aβ42 Peptide and IAPP Physically Interact in a Yeast-Based Assay |
title_sort | aβ42 peptide and iapp physically interact in a yeast-based assay |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10531723/ https://www.ncbi.nlm.nih.gov/pubmed/37762425 http://dx.doi.org/10.3390/ijms241814122 |
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