TY - JOUR

T1 - The Aβ42 Peptide and IAPP Physically Interact in a Yeast-Based Assay

AU - Kachkin, Daniel V.

AU - Lashkul, Veronika V.

AU - Gorsheneva, Natalia A.

AU - Fedotov, Sergey A.

AU - Rubel, Maria S.

AU - Chernoff, Yury O.

AU - Rubel, Aleksandr A.

PY - 2023/9/15

Y1 - 2023/9/15

N2 - 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.

AB - 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.

KW - амилоидозы

KW - болезнь Альцгеймера

KW - диабет 2 типа

KW - белок-белковые взаимодействия

KW - агрегация белков

KW - амилоид бета

KW - PrP

KW - амилин

KW - FRET

KW - Humans

KW - Alzheimer Disease

KW - Amyloid beta-Peptides

KW - Diabetes Mellitus, Type 2

KW - Saccharomyces cerevisiae

KW - Islet Amyloid Polypeptide

UR - https://www.mendeley.com/catalogue/6907986d-5c0d-377a-8ead-4539e992951a/

U2 - 10.3390/ijms241814122

DO - 10.3390/ijms241814122

M3 - Article

C2 - 37762425

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 18

M1 - 14122

ER -