Molecular interaction between type 2 diabetes and Alzheimer's disease through cross-seeding of protein misfolding.

ABSTRACT: Numerous epidemiological studies have shown a significantly higher risk for development of Alzheimer's disease (AD) in patients affected by type 2 diabetes (T2D), but the molecular mechanism responsible for this association is presently unknown. Both diseases are considered protein misfolding disorders associated with the accumulation of protein aggregates; amyloid-beta (Aβ) and tau in the brain during AD, and islet amyloid polypeptide (IAPP) in pancreatic islets in T2D. Formation and accumulation of these proteins follows a seeding-nucleation model, where a misfolded aggregate or 'seed' promotes the rapid misfolding and aggregation of the native protein. Our underlying hypothesis is that misfolded IAPP produced in T2D potentiates AD pathology by cross-seeding Aβ, providing a molecular exp

SUBMITTER: Moreno-Gonzalez I 

PROVIDER: S-EPMC5495631 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature