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.
Highlights
Alzheimer’s disease (AD) is a progressive, irreversible, neurodegenerative disorder characterized by the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs) within the brain
The extract obtained from L. vannamei was confirmed to be composed of a heterogenous mixture of GAGs, including chondroitin sulphate (CS), heparan sulphate (HS) and dermatan sulphate (DS), by NMR spectroscopy. 1H-13C heteronuclear single-quantum correlation (HSQC)
When analysed by agarose gel electrophoresis, both L. vannamei fractions were observed to contain a major band with a migration distance corresponding to heparin/HS and a
Summary
Alzheimer’s disease (AD) is a progressive, irreversible, neurodegenerative disorder characterized by the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs) within the brain.
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