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dc.contributor.authorCaruana, Mario-
dc.contributor.authorNeuner, Johanna-
dc.contributor.authorHogen, Tobias-
dc.contributor.authorSchmidt, Felix-
dc.contributor.authorFamp, Frits-
dc.contributor.authorScerri, Charles-
dc.contributor.authorGiese, Armin-
dc.contributor.authorVassallo, Neville-
dc.identifier.citationCaruana, M., Neuner, J., Hogen, T., Schmidt, F., Famp, F., Scerri, C., Giese, A., & Vassallo, N. (2012). Polyphenolic compounds are novel protective agents against lipid membrane damage by alpha-synuclein aggregates in vitro. Biochimica et Biophysica Acta (BBA) – Biomembranes, 1818(11), 2502-2510.en_GB
dc.description.abstractCumulative evidence now suggests that the abnormal aggregation of the protein α-synuclein (αS) is a critical factor in triggering neurodegeneration in Parkinson's disease (PD). In particular, a fundamental pathogenetic mechanism appears to involve targeting of neuronal membranes by soluble oligomeric intermediates of αS, leading to their disruption or permeabilisation. Therefore, a model assay was developed in which fluorophore-loaded unilamellar vesicles were permeabilised by soluble oligomers, the latter formed by aggregation of human recombinant αS protein. The αS oligomers induced an impairment of membrane integrity similar to that of the pore-forming bacterial peptide gramicidin. The lipid vesicle permeabilisation assay was then utilised to screen 11 natural polyphenolic compounds, 8 synthetic N′-benzylidene-benzohydrazide compounds and black tea extract for protection against membrane damage by wild-type and mutant (A30P, A53T) synuclein aggregates. A select group of potent inhibitory compounds included apigenin, baicalein, morin, nordihydroguaiaretic acid, and black tea extract. Structure–activity analysis further suggests that a 5,7-dihydroxy-chromen-4-one moiety appears to be favourable for the inhibition reaction. In conclusion, we have identified a group of polyphenols that can effectively hinder membrane damage by αS aggregates. These may serve as a viable source of lead compounds for the development and design of novel therapeutic agents in PD.en_GB
dc.publisherElsevier BVen_GB
dc.subjectParkinson's diseaseen_GB
dc.titlePolyphenolic compounds are novel protective agents against lipid membrane damage by alpha-synuclein aggregates in vitroen_GB
dc.rights.holderThe 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.publication.titleBiochimica et Biophysica Acta (BBA) - Biomembranesen_GB
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Scholarly Works - FacM&SPB

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