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Effects of Deferasirox in Alzheimer’s Disease and Tauopathy Animal Models

The accumulation of iron may contribute to Alzheimer’s disease (AD) and other tauopathies. The iron chelator desferrioxamine slows disease progression in AD patients. However, desferrioxamine requires injection, which is inconvenient and may hinder compliance. We therefore tested an oral iron chelat...

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Autores principales: Kwan, Ping, Ho, Amy, Baum, Larry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945800/
https://www.ncbi.nlm.nih.gov/pubmed/35327557
http://dx.doi.org/10.3390/biom12030365
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author Kwan, Ping
Ho, Amy
Baum, Larry
author_facet Kwan, Ping
Ho, Amy
Baum, Larry
author_sort Kwan, Ping
collection PubMed
description The accumulation of iron may contribute to Alzheimer’s disease (AD) and other tauopathies. The iron chelator desferrioxamine slows disease progression in AD patients. However, desferrioxamine requires injection, which is inconvenient and may hinder compliance. We therefore tested an oral iron chelator, desferasirox (Exjade), in transgenic animal models. Tg2576 mice overexpress the mutant human APP protein and produce the Aβ peptide. JNPL3 mice (Tau/Tau) overexpress the mutant human tau protein. Crossing these produced APP/Tau mice, overexpressing both APP and tau. Treating the three models with 1.6 mg deferasirox thrice weekly from age 8 to 14 months did not affect memory as measured by contextual fear conditioning or motor function as measured by rotarod, but tended to decrease hyperphosphorylated tau as measured by AT8 immunohistochemistry and immunoblotting. Deferasirox might act by decreasing iron, which aggregates tau, or directly binding tau to inhibit aggregation.
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spelling pubmed-89458002022-03-25 Effects of Deferasirox in Alzheimer’s Disease and Tauopathy Animal Models Kwan, Ping Ho, Amy Baum, Larry Biomolecules Brief Report The accumulation of iron may contribute to Alzheimer’s disease (AD) and other tauopathies. The iron chelator desferrioxamine slows disease progression in AD patients. However, desferrioxamine requires injection, which is inconvenient and may hinder compliance. We therefore tested an oral iron chelator, desferasirox (Exjade), in transgenic animal models. Tg2576 mice overexpress the mutant human APP protein and produce the Aβ peptide. JNPL3 mice (Tau/Tau) overexpress the mutant human tau protein. Crossing these produced APP/Tau mice, overexpressing both APP and tau. Treating the three models with 1.6 mg deferasirox thrice weekly from age 8 to 14 months did not affect memory as measured by contextual fear conditioning or motor function as measured by rotarod, but tended to decrease hyperphosphorylated tau as measured by AT8 immunohistochemistry and immunoblotting. Deferasirox might act by decreasing iron, which aggregates tau, or directly binding tau to inhibit aggregation. MDPI 2022-02-25 /pmc/articles/PMC8945800/ /pubmed/35327557 http://dx.doi.org/10.3390/biom12030365 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Kwan, Ping
Ho, Amy
Baum, Larry
Effects of Deferasirox in Alzheimer’s Disease and Tauopathy Animal Models
title Effects of Deferasirox in Alzheimer’s Disease and Tauopathy Animal Models
title_full Effects of Deferasirox in Alzheimer’s Disease and Tauopathy Animal Models
title_fullStr Effects of Deferasirox in Alzheimer’s Disease and Tauopathy Animal Models
title_full_unstemmed Effects of Deferasirox in Alzheimer’s Disease and Tauopathy Animal Models
title_short Effects of Deferasirox in Alzheimer’s Disease and Tauopathy Animal Models
title_sort effects of deferasirox in alzheimer’s disease and tauopathy animal models
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945800/
https://www.ncbi.nlm.nih.gov/pubmed/35327557
http://dx.doi.org/10.3390/biom12030365
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