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Reciprocal Molecular Interactions between the Aβ Peptide Linked to Alzheimer's Disease and Insulin Linked to Diabetes Mellitus Type II

Luo, Jinghui and Wärmländer, Sebastian K. T. S. and Gräslund, Astrid and Abrahams, Jan Pieter. (2016) Reciprocal Molecular Interactions between the Aβ Peptide Linked to Alzheimer's Disease and Insulin Linked to Diabetes Mellitus Type II. ACS Chemical Neuroscience , 7 (3). pp. 269-274.

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Official URL: http://edoc.unibas.ch/54056/

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Abstract

Clinical studies indicate diabetes mellitus type II (DM) doubles the risk that a patient will also develop Alzheimer's disease (AD). DM is caused by insulin resistance and a relative lack of active insulin. AD is characterized by the deposition of amyloid β (Aβ) peptide fibrils. Prior to fibrillating, Aβ forms intermediate, prefibrillar oligomers, which are more cytotoxic than the mature Aβ fibrils. Insulin can also form amyloid fibrils. In vivo studies have revealed that insulin promotes the production of Aβ, and that soluble Aβ competes with insulin for the insulin receptor. Here, we report that monomeric insulin interacted with soluble Aβ and that both molecules reciprocally slowed down the aggregation kinetics of the other. Prefibrillar oligomers of Aβ that eventually formed in the presence of insulin were less cytotoxic than Aβ oligomers formed in the absence of insulin. Mature Aβ fibrils induced fibrillation of soluble insulin, but insulin aggregates did not promote Aβ fibrillation. Our study indicates that direct molecular interactions between insulin and Aβ may contribute to the strong link between DM and AD.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Nano-diffraction of Biological Specimen (Abrahams)
UniBasel Contributors:Abrahams, Jan Pieter
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Chemical Society
e-ISSN:1948-7193
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:25 Oct 2017 15:15
Deposited On:25 Oct 2017 15:15

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