| Autor: |
Mycroft-West CJ; Molecular & Structural Biosciences, School of Life Sciences, Keele University, Huxley Building, Keele, Staffordshire ST5 5BG, UK., Devlin AJ; Molecular & Structural Biosciences, School of Life Sciences, Keele University, Huxley Building, Keele, Staffordshire ST5 5BG, UK., Cooper LC; Molecular & Structural Biosciences, School of Life Sciences, Keele University, Huxley Building, Keele, Staffordshire ST5 5BG, UK., Guimond SE; School of Medicine, Keele University, Huxley Building, Keele, Staffordshire ST5 5BG, UK., Procter P; Molecular & Structural Biosciences, School of Life Sciences, Keele University, Huxley Building, Keele, Staffordshire ST5 5BG, UK., Guerrini M; Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni, via G. Colombo 81, 20133 Milan, Italy., Miller GJ; School of Chemistry, Keele University, Huxley Building, Keele, Staffordshire ST5 5BG, UK., Fernig DG; Department of Biochemistry and Systems Biology, ISMIB, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK., Yates EA; Department of Biochemistry and Systems Biology, ISMIB, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK., Lima MA; Molecular & Structural Biosciences, School of Life Sciences, Keele University, Huxley Building, Keele, Staffordshire ST5 5BG, UK., Skidmore MA; Molecular & Structural Biosciences, School of Life Sciences, Keele University, Huxley Building, Keele, Staffordshire ST5 5BG, UK.; Department of Biochemistry and Systems Biology, ISMIB, University of Liverpool, Crown Street, Liverpool L69 7ZB, UK. |
| Abstrakt: |
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. |
