Document Type

Journal Article

Publication Title

International Journal of Molecular Sciences

Volume

23

Issue

24

PubMed ID

36555450

Publisher

MDPI

School

Centre for Precision Health / School of Medical and Health Sciences

RAS ID

53098

Comments

Woodfield, A., Gonzales, T., Helmerhorst, E., Laws, S., Newsholme, P., Porter, T., & Verdile, G. (2022). Current insights on the use of insulin and the potential use of insulin mimetics in targeting insulin signalling in Alzheimer’s disease. International Journal of Molecular Sciences, 23(24), Article 15811. https://doi.org/10.3390/ijms232415811

Abstract

Alzheimer’s disease (AD) and type 2 diabetes (T2D) are chronic diseases that share several pathological mechanisms, including insulin resistance and impaired insulin signalling. Their shared features have prompted the evaluation of the drugs used to manage diabetes for the treatment of AD. Insulin delivery itself has been utilized, with promising effects, in improving cognition and reducing AD related neuropathology. The most recent clinical trial involving intranasal insulin reported no slowing of cognitive decline; however, several factors may have impacted the trial outcomes. Long-acting and rapid-acting insulin analogues have also been evaluated within the context of AD with a lack of consistent outcomes. This narrative review provided insight into how targeting insulin signalling in the brain has potential as a therapeutic target for AD and provided a detailed update on the efficacy of insulin, its analogues and the outcomes of human clinical trials. We also discussed the current evidence that warrants the further investigation of the use of the mimetics of insulin for AD. These small molecules may provide a modifiable alternative to insulin, aiding in developing drugs that selectively target insulin signalling in the brain with the aim to attenuate cognitive dysfunction and AD pathologies.

DOI

10.3390/ijms232415811

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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