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DC Field | Value | Language |
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dc.date.accessioned | 2019-02-08T13:41:13Z | - |
dc.date.available | 2019-02-08T13:41:13Z | - |
dc.date.issued | 2010 | - |
dc.identifier.citation | Gauci A. (2010). Identification of natural polyphenols and plant extracts as potent inhibitors of lipid membrane destabilisation by amyloid-beta peptide (1-42) (Master's dissertation). | en_GB |
dc.identifier.uri | https://www.um.edu.mt/library/oar//handle/123456789/39755 | - |
dc.description | M.SC.PATHOLOGY | en_GB |
dc.description.abstract | Amyloid-beta (Aβ) aggregation is a recognised key process in the pathogenesis of Alzheimer's Disease {AD}, the most common age-related neurodegenerative disorder. Misfolded Aβ peptides self-assemble sequentially into oligomers, protofibrils and fibrils; current evidence points to oligomers as being the primary neurotoxic Aβ species, especially because they are highly disruptive to lipid membranes. Hence the aim was to explore whether small-molecule compounds and bioactive natural extracts can inhibit aggregated Aβ from damaging lipid membranes. Using a combination of fluorophore-based lipid vesicle assays, Thioflavin T assays and immunoblotting, a robust protocol for Aβ(1-42) peptide aggregation into a range of ollgomers (20-220 kDa) having 30-40% liposomal toxicity was first established. Assays using liposomes loaded with FITC-dextran molecules of different sizes confirmed that the Aβ oligomers efficiently permeabilised the vesicle membranes. Next, 15 small-molecule polyphenolic compounds, 8 N'-benzylidene-benzohydrazide (NBB) compounds, 7 diphenylpyrazole (DPP) compounds, and 4 plant extracts were assessed for their ability to antagonise liposome permeabilisation by the Aβ(1-42) oligomers. Essentially, it was found that black tea extract, apigenin, baicalein and nordihydroguaiaretic acid (NDGA) potently inhibited lipid membrane damage by aggregated Aβ to < 30% of the control value (permeabilisation caused by Aβ). Solubilised extract from the marine plant Padina pavonica, scutellarein and synthetic DPP compound nr. 15 inhibited liposome permeabilisation by Aβ aggregates to "'40%. Interestingly, apigenin, baicalein and scutellarein are flavones and both NDGA and DPP nr. 15 are symmetrical molecules of similar length having a benzene ring at each end of the molecule. Synergism was found when pairwise combinations of DPP15, apigenin and NDGA were performed. Indeed, detailed structure-function analysis of our data could assist in the identification of common chemical scaffolds for inhibition of oligomer toxicity in neurodegenerative amyloidoses. | en_GB |
dc.language.iso | en | en_GB |
dc.rights | info:eu-repo/semantics/restrictedAccess | en_GB |
dc.subject | Polyphenols | en_GB |
dc.subject | Plant extracts | en_GB |
dc.subject | Lipid membranes | en_GB |
dc.subject | Amyloid beta-protein | en_GB |
dc.title | Identification of natural polyphenols and plant extracts as potent inhibitors of lipid membrane destabilisation by amyloid-beta peptide (1-42) | en_GB |
dc.type | masterThesis | en_GB |
dc.rights.holder | The copyright of this work belongs to the author(s)/publisher. The rights of this work are as defined by the appropriate Copyright Legislation or as modified by any successive legislation. Users may access this work and can make use of the information contained in accordance with the Copyright Legislation provided that the author must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the prior permission of the copyright holder | en_GB |
dc.publisher.institution | University of Malta | en_GB |
dc.publisher.department | Faculty of Medicine and Surgery. | en_GB |
dc.contributor.supervisor | Vassallo, Neville | - |
dc.description.reviewed | N/A | en_GB |
dc.contributor.creator | Gauci, Alison | - |
Appears in Collections: | Dissertations - FacM&S - 2010 Dissertations - FacM&SPat - 2010 |
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Gauci_Alison J_Identification of natural polyphenols and plant extracts as potent inhibitors of lipid membrane destabilisation by amyloid-beta peptide 1-42.pdf Restricted Access | 12.43 MB | Adobe PDF | View/Open Request a copy |
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