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Mycroft-West, Courtney J., Cooper, Lynsay C 
ORCID: 0000-0002-5100-5261, Devlin, Anthony J., Procter, Patricia, Guimond, Scott E., Guerrini, Marco, Fernig, David G., Lima, Marcelo A., Yates, Edwin A. and Skidmore, Mark A.
(2019)
A glycosaminoglycan extract from Portunus pelagicus inhibits BACE1, the β secretase implicated in Alzheimer’s disease.
Marine Drugs, 17 (5).
p. 293.
doi:10.3390/md17050293
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Text (Published version)
10070-Cooper-(2019)-A-glycosaminoglycan-extract-from-Portanus-pelagicus.pdf - Published Version Available under License Creative Commons Attribution 4.0. Download (3MB) | Preview |
Abstract
Therapeutic options for Alzheimer’s disease, the most common form of dementia, are currently restricted to palliative treatments. The glycosaminoglycan heparin, widely used as a clinical anticoagulant, has previously been shown to inhibit the Alzheimer’s disease-relevant β-secretase 1 (BACE1). Despite this, the deployment of pharmaceutical heparin for the treatment of Alzheimer’s disease is largely precluded by its potent anticoagulant activity. Furthermore, ongoing concerns regarding the use of mammalian-sourced heparins, primarily due to prion diseases and religious beliefs hinder the deployment of alternative heparin-based therapeutics. A marine-derived, heparan sulphate-containing glycosaminoglycan extract, isolated from the crab Portunus pelagicus, was identified to inhibit human BACE1 with comparable bioactivity to that of mammalian heparin (IC50 = 1.85 μg mL−1 (R2 = 0.94) and 2.43 μg mL−1 (R2 = 0.93), respectively), while possessing highly attenuated anticoagulant activities. The results from several structural techniques suggest that the interactions between BACE1 and the extract from P. pelagicus are complex and distinct from those of heparin.
| Item Type: | Article |
|---|---|
| Article Type: | Article |
| Uncontrolled Keywords: | Alzheimer’s disease; Amyloid-β; BACE1; β-secretase; Glycosaminoglycan; Heparan sulphate; Heparin; Portunus pelagicus |
| Subjects: | Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica |
| Divisions: | Schools and Research Institutes > School of Education and Science |
| Research Priority Areas: | Place, Environment and Community |
| Depositing User: | Lynsay Cooper |
| Date Deposited: | 24 Aug 2021 15:39 |
| Last Modified: | 31 Aug 2023 08:58 |
| URI: | https://eprints.glos.ac.uk/id/eprint/10070 |
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