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 i...

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Bibliographic Details
Published in:	Marine drugs 2021-04, Vol.19 (4), p.203
Main Authors:	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
Format:	Article
Language:	eng
Subjects:	Acids Aetiology Alzheimer's disease Alzheimers disease Amyloid Precursor Protein Secretases - antagonists & inhibitors Amyloid Precursor Protein Secretases - metabolism amyloid-β Animals Anticoagulants Aspartic Acid Endopeptidases - antagonists & inhibitors Aspartic Acid Endopeptidases - metabolism BACE1 Blood Coagulation - drug effects chondroitin sulfate Crustaceans Diseases Drug development Drugs Enzyme Stability glycosaminoglycan Glycosaminoglycans Glycosaminoglycans - isolation & purification Glycosaminoglycans - pharmacology Heparin Humans Ions Litopenaeus vannamei Medical treatment Molecular weight Neurodegenerative diseases Oxidative stress Partial Thromboplastin Time Penaeidae - metabolism Peptides Pharmaceuticals Phosphorylation Protease Inhibitors - isolation & purification Protease Inhibitors - pharmacology Proteins Prothrombin Time Secretase Spectrum analysis Tau protein β-Amyloid β-secretase β-Site APP-cleaving enzyme 1
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Summary:	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 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.
ISSN:	1660-3397 1660-3397