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Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease β Secretase, BACE1

Only palliative therapeutic options exist for the treatment of Alzheimer’s Disease; no new successful drug candidates have been developed in over 15 years. The widely used clinical anticoagulant heparin has been reported to exert beneficial effects through multiple pathophysiological pathways involv...

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Autores principales: Mycroft-West, Courtney J., Devlin, Anthony J., Cooper, Lynsay C., Guimond, Scott E., Procter, Patricia, Guerrini, Marco, Miller, Gavin J., Fernig, David G., Yates, Edwin A., Lima, Marcelo A., Skidmore, Mark A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067017/
https://www.ncbi.nlm.nih.gov/pubmed/33916819
http://dx.doi.org/10.3390/md19040203
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author Mycroft-West, Courtney J.
Devlin, Anthony J.
Cooper, Lynsay C.
Guimond, Scott E.
Procter, Patricia
Guerrini, Marco
Miller, Gavin J.
Fernig, David G.
Yates, Edwin A.
Lima, Marcelo A.
Skidmore, Mark A.
author_facet Mycroft-West, Courtney J.
Devlin, Anthony J.
Cooper, Lynsay C.
Guimond, Scott E.
Procter, Patricia
Guerrini, Marco
Miller, Gavin J.
Fernig, David G.
Yates, Edwin A.
Lima, Marcelo A.
Skidmore, Mark A.
author_sort Mycroft-West, Courtney J.
collection PubMed
description Only palliative therapeutic options exist for the treatment of Alzheimer’s Disease; no new successful drug candidates have been developed in over 15 years. The widely used clinical anticoagulant heparin has been reported to exert beneficial effects through multiple pathophysiological pathways involved in the aetiology of Alzheimer’s Disease, for example, amyloid peptide production and clearance, tau phosphorylation, inflammation and oxidative stress. Despite the therapeutic potential of heparin as a multi-target drug for Alzheimer’s disease, the repurposing of pharmaceutical heparin is proscribed owing to the potent anticoagulant activity of this drug. Here, a heterogenous non-anticoagulant glycosaminoglycan extract, obtained from the shrimp Litopenaeus vannamei, was found to inhibit the key neuronal β-secretase, BACE1, displaying a more favorable therapeutic ratio compared to pharmaceutical heparin when anticoagulant activity is considered.
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spelling pubmed-80670172021-04-25 Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease β Secretase, BACE1 Mycroft-West, Courtney J. Devlin, Anthony J. Cooper, Lynsay C. Guimond, Scott E. Procter, Patricia Guerrini, Marco Miller, Gavin J. Fernig, David G. Yates, Edwin A. Lima, Marcelo A. Skidmore, Mark A. Mar Drugs Article Only palliative therapeutic options exist for the treatment of Alzheimer’s Disease; no new successful drug candidates have been developed in over 15 years. The widely used clinical anticoagulant heparin has been reported to exert beneficial effects through multiple pathophysiological pathways involved in the aetiology of Alzheimer’s Disease, for example, amyloid peptide production and clearance, tau phosphorylation, inflammation and oxidative stress. Despite the therapeutic potential of heparin as a multi-target drug for Alzheimer’s disease, the repurposing of pharmaceutical heparin is proscribed owing to the potent anticoagulant activity of this drug. Here, a heterogenous non-anticoagulant glycosaminoglycan extract, obtained from the shrimp Litopenaeus vannamei, was found to inhibit the key neuronal β-secretase, BACE1, displaying a more favorable therapeutic ratio compared to pharmaceutical heparin when anticoagulant activity is considered. MDPI 2021-04-03 /pmc/articles/PMC8067017/ /pubmed/33916819 http://dx.doi.org/10.3390/md19040203 Text en © 2021 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 Article
Mycroft-West, Courtney J.
Devlin, Anthony J.
Cooper, Lynsay C.
Guimond, Scott E.
Procter, Patricia
Guerrini, Marco
Miller, Gavin J.
Fernig, David G.
Yates, Edwin A.
Lima, Marcelo A.
Skidmore, Mark A.
Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease β Secretase, BACE1
title Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease β Secretase, BACE1
title_full Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease β Secretase, BACE1
title_fullStr Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease β Secretase, BACE1
title_full_unstemmed Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease β Secretase, BACE1
title_short Glycosaminoglycans from Litopenaeus vannamei Inhibit the Alzheimer’s Disease β Secretase, BACE1
title_sort glycosaminoglycans from litopenaeus vannamei inhibit the alzheimer’s disease β secretase, bace1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067017/
https://www.ncbi.nlm.nih.gov/pubmed/33916819
http://dx.doi.org/10.3390/md19040203
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