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Updated: Jun 27, 2026

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
The irreversible binding of amyloid peptide substrates to insulin-degrading enzyme: a biological perspective
Matías B de Tullio1, Laura Morelli, Eduardo M Castaño
1Fundación Instituto Leloir-Instituto de Investigaciones Bioquímicas de Buenos Aires, CONICET, Buenos Aires, Argentina.
Abstract:
Insulin-degrading enzyme (IDE) is a conserved Zn(2+)metalloendopeptidase involved in insulin degradation and in the maintenance of brain steady-state levels of amyloid beta peptide (Abeta) of Alzheimer's disease (AD). Our recent demonstration that IDE and Abeta are capable of forming a stoichiometric and extremely stable complex raises several intriguing possibilities regarding the role of this unique protein-peptide interaction in physiological and pathological conditions. These include a protective cellular function of IDE as a "dead-end chaperone" alternative to its proteolytic activity and the potential impact of the irreversible binding of Abeta to IDE upon its role as a varicella zoster virus receptor. In a pathological context, the implications for insulin signaling and its relationship to AD pathogenesis are discussed. Moreover, our findings warrant further research regarding a possible general and novel interaction between amyloidogenic peptides and other Zn(2+)metallopeptidases with an IDE-like fold and a substrate conformation-dependent recognition mechanism.
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