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2 results on '"Anthony J Devlin"'

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

Author

Courtney J. Mycroft-West, Anthony J. Devlin, Lynsay C. Cooper, Scott E. Guimond, Patricia Procter, Marco Guerrini, Gavin J. Miller, David G. Fernig, Edwin A. Yates, Marcelo A. Lima, and Mark A. Skidmore

Subjects
Alzheimer’s disease, amyloid-β, BACE1, β-secretase, glycosaminoglycan, chondroitin sulfate, Biology (General), QH301-705.5
Abstract

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.

Published
2021
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2. A Glycosaminoglycan Extract from Portunus pelagicus Inhibits BACE1, the β Secretase Implicated in Alzheimer’s Disease

Author

Mark A. Skidmore, Lynsay C. Cooper, Marcelo A. Lima, Edwin A. Yates, Patricia Procter, Marco Guerrini, Courtney J. Mycroft-West, David G. Fernig, Anthony J. Devlin, and Scott E. Guimond

Subjects
Pharmaceutical Science, Disease, heparin, Pharmacology, Glycosaminoglycan, 0302 clinical medicine, heparan sulphate, Drug Discovery, Aspartic Acid Endopeptidases, β-secretase, Medicine, QD, Enzyme Inhibitors, lcsh:QH301-705.5, Pharmacology, Toxicology and Pharmaceutics (miscellaneous), Glycosaminoglycans, 0303 health sciences, biology, Anticoagulant, BACE1, Portunus pelagicus, Heparin, RC346, β secretase, Alzheimer’s disease, medicine.drug, RM, Brachyura, medicine.drug_class, amyloid-β, Article, RS, 03 medical and health sciences, Alzheimer Disease, glycosaminoglycan, Animals, Dementia, Beta (finance), IC50, 030304 developmental biology, business.industry, Anticoagulants, medicine.disease, biology.organism_classification, Enzyme Activation, lcsh:Biology (General), biology.protein, Amyloid Precursor Protein Secretases, business, Amyloid precursor protein secretase, 030217 neurology & neurosurgery, QD415
Abstract

Therapeutic options for Alzheimer&rsquo, 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&rsquo, s disease-relevant &beta, secretase 1 (BACE1). Despite this, the deployment of pharmaceutical heparin for the treatment of Alzheimer&rsquo, 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 &mu, g mL&minus, 1 (R2 = 0.94) and 2.43 &mu, 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.

Published
2019
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