Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.691390
Title: Interaction between the Alzheimer's peptide, beta-amyloid and lipid membrane
Author: Saurabh, Rahul
ISNI:       0000 0004 5917 9674
Awarding Body: University of Hull
Current Institution: University of Hull
Date of Award: 2015
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Abstract:
Alzheimer’s disease (AD) is a neurodegenerative disorder. The patho-physiological effects of amyloid beta (Aβ) may be mediated by Aβ-membrane interaction. However, the molecular mechanism of interaction between Aβ and neuronal membrane remains unknown. The aim of the study was to investigate the interaction of a toxic fragment of amyloid beta, Aβ₂₅-₃₅ with the lipid membrane model using model lipid bilayers and beta breaker peptide, KLVFF. Liquid ¹H NMR assay was used to investigate the aggregation properties of Aβ₂₅-₃₅. The sharp NMR peaks of Aβ₂₅-₃₅ appeared immediately after sample preparation and these peaks were lost after 24 hrs incubation. However, on addition of KLVFF to Aβ₂₅-₃₅, the amyloid peptide peaks remain unchanged even after long period of incubation. The data suggest that KLVFF has ability to inhibit the aggregation of Aβ₂₅-₃₅. Magic angle spinning solid state NMR were used to investigate the location and interaction of Aβ₂₅-₃₅ to lipid bilayers. NOESY cross-relaxation rates suggest that the soluble form of Aβ₂₅-₃₅ may interact predominantly with the lipid chains near glycerol region. The cholesterol molecules did not exhibit direct interaction with soluble Aβ₂₅-₃₅. However, cross relaxation rate data suggest that cholesterol may push the soluble Aβ₂₅-₃₅ towards the head region of lipid bilayers. The data indicates that soluble form of Aβ₂₅-₃₅ may enter into lipid bilayers and interact with phospholipids. ²H NMR was used to analyse the effect of Aβ₂₅-₃₅ on lipid phase behaviour. M₁ analysis and methyl splitting data were used to observe the phase transitions. Aβ₂₅-₃₅ lowers the lipid phase transitions temperature in presence and absence of cholesterol. The data suggest that the insoluble form of Aβ₂₅-₃₅ may develop the lipid order (stiffness) and thus lowers the phase transition temperature. The Aβ₂₅-₃₅ plus KLVFF with cholesterol may also significantly raise the phase transition temperature and also elongate the phase transition boundaries, indicating that cholesterol molecules may enhance the lipid order parameter. In conclusion, KLVFF may stop the amyloid beta aggregation either in solution or in the lipid bilayers. Cholesterol molecules may not interact directly with amyloid beta and it may also affect the location of amyloid beta in the lipid bilayers. The results of the study may be important to understand the interactions between Aβ and lipid bilayers which may act as new therapeutic strategies for the development of new drugs for amyloid diseases.
Supervisor: Lorch, Mark ; Archibald, Stephen J. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.691390  DOI: Not available
Keywords: Chemistry
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