Insights into Non-Proteolytic Inhibitory Mechanisms of Polymorphic Early-Stage Amyloid β Oligomers by Insulin Degrading Enzyme.

ABSTRACT: Insulin degrading enzyme (IDE) has been detected in the cerebrospinal fluid media and plays a role in encapsulating and degrading the amyloid β (Aβ) monomer, thus regulating the levels of Aβ monomers. The current work illustrates a first study by which IDE encapsulates polymorphic early-stage Aβ oligomers. The main goal of this study was to investigate the molecular mechanisms of IDE activity on the encapsulated early-stage Aβ dimers: fibril-like and random coil/α-helix dimers. Our work led to several findings. First, when the fibril-like Aβ dimer interacts with IDE-C domain, IDE does not impede the contact between the monomers, but plays a role as a 'dead-end' chaperone protein. Second, when the fibril-like Aβ dimer interacts with the IDE-N domain, IDE successfully impedes the contacts be

SUBMITTER: Abramov-Harpaz K 

PROVIDER: S-EPMC9776231 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature