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Title: Neuroprotective Effects of the Amylin Analog, Pramlintide, on Alzheimer's Disease Are Associated with Oxidative Stress Regulation Mechanisms
Author: Patrick, Sarah
Corrigan, Rachel
Grizzanti, Johna
Mey, Megan
Blair, Jeff
Pallàs i Llibería, Mercè, 1964-
Camins Espuny, Antoni
Lee, Hyoung-gon
Casadesús, Gemma
Keywords: Malaltia d'Alzheimer
Estrès oxidatiu
Alzheimer's disease
Oxidative stress
Issue Date: 16-Apr-2019
Publisher: IOS Press
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
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It is part of: Journal of Alzheimer's Disease, 2019, vol. 69, num. 1, p. 157.-168
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ISSN: 1387-2877
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

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