https://doi.org/10.1140/epjb/s10051-024-00796-z
Topical Review - Statistical and Nonlinear Physics
Insights from microcanonical thermostatistics into amylin analogues and amyloid-
cross-seeding
Universidade Tecnológica Federal do Paraná, Rua Cristo Rei 19, 85902-490, Toledo, PR, Brazil
Received:
2
March
2024
Accepted:
25
September
2024
Published online:
16
October
2024
Growing evidence from population studies and clinical observations strongly suggests a complex connection between major proteinopathies, to know, Type 2 diabetes (T2D) and Alzheimer’s disease (AD). People with T2D face a significantly higher risk of developing AD compared to those without diabetes. These two conditions share several key features, such as inflammation, oxidative stress, metabolic dysfunction, and the buildup of certain proteins known as beta-amyloid (A
42) and pancreatic islet amyloid polypeptide (IAPP or amylin). In AD, the brain develops characteristic senile plaques mainly composed of A42. Similarly, in individuals with T2D, the pancreas shows deposits of a protein called human amylin (hIAPP). The accumulation of these aggregated proteins in both the brain and pancreas has been associated with impaired cell function and even cell death. To gain molecular insight in the outset of such complex scenario, we perform microcanonical thermostatistics analysis of Monte Carlo simulations of A42 cross-seeded by hIAPP, or its biotechnological therapeutic analogous as Pramlintide. We find that while A42 is quite prone to cross-seed with hIAPP, and then to aggregate around that critical nuclei, this can be abolished for some of its analogues, which may possibly lead to alternative therapeutic approaches to T2D and AD.
Copyright comment Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
© The Author(s), under exclusive licence to EDP Sciences, SIF and Springer-Verlag GmbH Germany, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
