Short Amylin Receptor Antagonist Peptides Improve Memory Deficits in Alzheimer’s Disease Mouse Model

Authors

Rania Soudy, University of Alberta
Ryoichi Kimura, Sanyo- Onoda City University
Aarti Patel, University of Alberta
Wen Fu, University of Alberta
Kamaljit Kaur, Chapman UniversityFollow
David Westaway, University of Alberta
Jing Yang, University of Alberta
Jack Jhamandas, University of Alberta

Document Type

Article

Publication Date

7-29-2019

Abstract

Recent evidence supports involvement of amylin and the amylin receptor in the pathogenesis of Alzheimer’s disease (AD). We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12–14 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against Aβ toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY within the peptides is an essential sequence for preservation of the beneficial effects of the fragments that we report here and constitutes a new pharmacological target. These findings suggest that the amylin receptor antagonism may represent a novel therapy for AD.

Comments

This article was originally published in Scientific Reports, volume 9, issue 1, in 2019. DOI: 10.1038/s41598-019-47255-9

Recommended Citation

Soudy R, Kimura R, Patel A, et al. Short amylin receptor antagonist peptides improve memory deficits in Alzheimer’s disease mouse model. Sci. Rep. 2019;9(1):10942. doi:10.1038/s41598-019-47255-9

Copyright

The authors

Creative Commons License

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