Files
Document type
ArticleVersion
Published versionPublication date
All rights reserved
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/141842
Neuroprotective Effects of the Amylin Analog, Pramlintide, on Alzheimer's Disease Are Associated with Oxidative Stress Regulation Mechanisms
Journal Title
Director/Tutor
Journal ISSN
Volume Title
Related resource
Abstract
Administration of the recombinant analog of the pancreatic amyloid amylin, Pramlintide, has shown therapeutic benefits in aging and Alzheimer's disease (AD) models, both on cognition and amyloid-beta (Aβ) pathology. However, the neuroprotective mechanisms underlying Pramlintide benefits remain unclear. Given the early and critical role of oxidative stress in AD pathogenesis and the known ROS modulating function of amyloids we sought to determine whether Pramlintide's neuroprotective effects involve regulation of oxidative stress mechanisms. To address this we treated APP/PS1 transgenic mice with Pramlintide for 3 months, starting at 5.5 months prior to widespread AD pathology onset, and measured cognition (Morris Water Maze), AD pathology, and oxidative stress-related markers and enzymes in vivo. In vitro, we determined the ability of Pramlintide to modulate H2O2-induced oxidative stress levels. Our data show that Pramlintide improved cognitive function, altered amyloid-processing enzymes, reduced plaque burden in the hippocampus, and regulated endogenous antioxidant enzymes (MnSOD and GPx1) and the stress marker HO-1 in a location specific manner. In vitro, Pramlintide treatment in neuronal models reduced H2O2-induced endogenous ROS production and lipid peroxidation in a dose-dependent manner. Together, these results indicate that Pramlintide's benefits on cognitive function and pathology may involve antioxidant-like properties of this compoun
Subject (English)
Citation
Citation
PATRICK, Sarah, et al. Neuroprotective Effects of the Amylin Analog, Pramlintide, on Alzheimer's Disease Are Associated with Oxidative Stress Regulation Mechanisms. Journal of Alzheimer's Disease. 2019. Vol. 69, num. 1, pags. 157. ISSN 1387-2877. [consulted: 17 of June of 2026]. Available at: https://hdl.handle.net/2445/141842