Reciprocal Molecular Interactions between the A beta Peptide Linked to Alzheimer's Disease and Insulin Linked to Diabetes Mellitus Type II
Number of Authors: 4
2016 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 7, no 3, 269-274 p.Article in journal (Refereed) Published
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 beta (A beta) peptide fibrils. Prior to fibrillating, A beta forms intermediate, prefibrillar oligomers, which are more cytotoxic than the mature A beta fibrils. Insulin can also form amyloid fibrils. In vivo studies have revealed that insulin promotes the production of A beta, and that soluble A beta competes with insulin for the insulin receptor. Here, we report that monomeric insulin interacted with soluble A beta and that both molecules reciprocally slowed down the aggregation kinetics of the other. Prefibrillar oligomers of A beta that eventually formed in the presence of insulin were less cytotoxic than A beta oligomers formed in the absence of insulin. Mature A beta fibrils induced fibrillation of soluble insulin, but insulin aggregates did not promote A beta fibrillation. Our study indicates that direct molecular interactions between insulin and A beta may contribute to the strong link between DM and AD.
Place, publisher, year, edition, pages
2016. Vol. 7, no 3, 269-274 p.
Amyloid beta peptides, Alzheimer's disease, insulin, diabetes mellitus type II, cross amyloid interaction, fibrillation
Biological Sciences Neurosciences
IdentifiersURN: urn:nbn:se:su:diva-129624DOI: 10.1021/acschemneuro.5b00325ISI: 000372479600002PubMedID: 26785771OAI: oai:DiVA.org:su-129624DiVA: diva2:925553