Mycroft-West, CJ, Cooper, LC, Devlin, AJ, Procter, P, Guimond, SE, Guerrini, M, Fernig, DG, Lima, MA, Yates, EA and Skidmore, MA (2019) A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer’s Disease. Marine Drugs, 17 (5). 293 -293.

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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
Additional Information: This is the final published version of the article (version of record). It first appeared online via MDPI at https://doi.org/10.3390/md17050293 - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: Alzheimer’s disease, amyloid-β, BACE1, β-secretase, glycosaminoglycan, heparan sulphate, heparin, Portunus pelagicus
Subjects: Q Science > QD Chemistry > QD415 Biochemistry
R Medicine > RC Internal medicine > RC346 Neurology. Diseases of the nervous system, including speech disorders
R Medicine > RS Pharmacy and materia medica
Divisions: Faculty of Natural Sciences > School of Life Sciences
Depositing User: Symplectic
Date Deposited: 22 May 2019 11:04
Last Modified: 22 May 2019 11:11
URI: http://eprints.keele.ac.uk/id/eprint/6373

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