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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Veröffentlicht in:	Marine drugs Jg. 19; H. 4; S. 203
Hauptverfasser:	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:	Journal Article
Sprache:	Englisch
Veröffentlicht:	Switzerland MDPI AG 03.04.2021 MDPI
Schlagworte:	Acids Aetiology Alzheimer's disease amyloid Amyloid Precursor Protein Secretases - antagonists & inhibitors Amyloid Precursor Protein Secretases - metabolism amyloid-β Animals anticoagulant activity Anticoagulants Aspartic Acid Endopeptidases - antagonists & inhibitors Aspartic Acid Endopeptidases - metabolism BACE1 Blood Coagulation - drug effects chondroitin sulfate Crustaceans Diseases Drug development Drugs Enzyme Stability etiology glycosaminoglycan Glycosaminoglycans Glycosaminoglycans - isolation & purification Glycosaminoglycans - pharmacology Heparin Humans inflammation Ions Litopenaeus vannamei Molecular weight Neurodegenerative diseases neurons Oxidative stress Partial Thromboplastin Time Penaeidae - metabolism Peptides Pharmaceuticals Phosphorylation Protease Inhibitors - isolation & purification Protease Inhibitors - pharmacology Proteins Prothrombin Time Secretase shrimp Spectrum analysis Tau protein therapeutics β-Amyloid β-secretase β-Site APP-cleaving enzyme 1 BACE1 heparin Alzheimer’s disease chondroitin sulfate amyloid-β heparan sulphate β-secretase Litopenaeus vannamei glycosaminoglycan
ISSN:	1660-3397, 1660-3397
Online-Zugang:	Volltext
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1660-3397 1660-3397
DOI:	10.3390/md19040203