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dc.contributor.authorBorger, Eva
dc.contributor.authorAitken, Laura
dc.contributor.authorMuirhead, Kirsty Elizabeth Adair
dc.contributor.authorAllen, Zoe Eleanor
dc.contributor.authorAinge, James Alexander
dc.contributor.authorConway, Stuart
dc.contributor.authorGunn-Moore, Frank J
dc.date.accessioned2012-02-01T00:50:03Z
dc.date.available2012-02-01T00:50:03Z
dc.date.issued2011-08
dc.identifier8267012
dc.identifierc85fa05f-b1a0-4624-9cef-b370dc8cc897
dc.identifier79960868236
dc.identifier.citationBorger , E , Aitken , L , Muirhead , K E A , Allen , Z E , Ainge , J A , Conway , S & Gunn-Moore , F J 2011 , ' Mitochondrial β-amyloid in Alzheimer's disease ' , Biochemical Society Transactions , vol. 39 , no. 4 , pp. 868-873 . https://doi.org/10.1042/BST0390868en
dc.identifier.issn0300-5127
dc.identifier.otherORCID: /0000-0003-3422-3387/work/34730450
dc.identifier.otherORCID: /0000-0003-4965-2969/work/30767005
dc.identifier.otherORCID: /0000-0001-7259-4491/work/31318400
dc.identifier.otherORCID: /0000-0002-0007-1533/work/60428115
dc.identifier.urihttps://hdl.handle.net/10023/2250
dc.descriptionThis research is supported by Alzheimer's Research UK, the Wellcome Trust and the Biotechnology and Biological Sciences Research Council.en
dc.description.abstractIt is well established that the intracellular accumulation of beta-amyloid is associated with Alzheimer’s disease and that this accumulation is toxic to neurons. The precise mechanism by which this toxicity occurs is not well understood, however, identifying the causes of this toxicity is an essential step in developing treatments for Alzheimer’s disease. One intracellular location where the accumulation of beta-amyloid can have a major effect is within mitochondria has identified mitochondrial proteins that act as binding sites for beta-amyloid and when binding occurs a toxic response results. For one of these identified sites, an enzyme known as ‘ABAD’, we have identified the changes in gene expression in the brain cortex following beta-amyloid accumulation within mitochondria. Specifically, we have identified two proteins that are upregulated in the brains of transgenic animal models for Alzheimer’s disease but also human sufferers. The increased expression of these proteins demonstrates the complex and counter-acting pathways that are activated in Alzheimer’s disease. Previous studies have identified the approximate contact sites between ABAD and beta-amyloid, and based on these observations we have shown that using a modified peptide approach, it is possible to reverse the expression of these two proteins in living transgenic animals and also recover both mitochondrial and behavioural deficits. This indicates that the ABAD-beta-amyloid interaction is potentially an interesting target for therapeutic intervention. To explore this further we used a fluorescing substrate mimic to measure the activity of ABAD within living cells, and in addition we have identified chemical fragments that bind to ABAD, by using a thermal shift assay.
dc.format.extent345245
dc.language.isoeng
dc.relation.ispartofBiochemical Society Transactionsen
dc.subjectAlzheimer's diseaseen
dc.subjectMitochondrial dysfunctionen
dc.subjectIntracellular Aβen
dc.subjectABADen
dc.subjectCHANAen
dc.subjectCyclophilin Den
dc.subjectQP Physiologyen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.subject.lccQPen
dc.titleMitochondrial β-amyloid in Alzheimer's diseaseen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Institute of Behavioural and Neural Sciencesen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. School of Psychology and Neuroscienceen
dc.identifier.doi10.1042/BST0390868
dc.description.statusPeer revieweden
dc.date.embargoedUntil2012-02-01


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