Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/27756
Title: Mitochondrial membrane permeabilisation by amyloid aggregates and protection by polyphenols
Authors: Camilleri, Angelique
Zarb, Claire
Caruana, Mario
Ostermeier, Ulrike
Ghio, Stephanie
Hogen, Tobias
Schmidt, Felix
Giese, Armin
Vassallo, Neville
Keywords: Amyloid beta-protein
Alpha-synuclein
Mitochondrial membranes
Cardiolipin
Polyphenols
Tau proteins
Issue Date: 2013
Publisher: Elsevier BV
Citation: Camilleri, A., Zarb, C., Caruana, M., Ostermeier, U., Ghio, S., Hogen, T.,… Vassallo, N. (2013). Mitochondrial membrane permeabilisation by amyloid aggregates and protection by polyphenols. Biochimica et Biophysica Acta (BBA) – Biomembranes, 1828(11), 2532-2543.
Abstract: Alzheimer's disease and Parkinson's disease are neurodegenerative disorders characterised by the misfolding of proteins into soluble prefibrillar aggregates. These aggregate complexes disrupt mitochondrial function, initiating a pathophysiological cascade leading to synaptic and neuronal degeneration. In order to explore the interaction of amyloid aggregates with mitochondrial membranes, we made use of two in vitro model systems, namely: (i) lipid vesicles with defined membrane compositions that mimic those of mitochondrial membranes, and (ii) respiring mitochondria isolated from neuronal SH-SY5Y cells. External application of soluble prefibrillar forms, but not monomers, of amyloid-beta (Aβ42 peptide), wild-type α-synuclein (α-syn), mutant α-syn (A30P and A53T) and tau-441 proteins induced a robust permeabilisation of mitochondrial-like vesicles, and triggered cytochrome c release (CCR) from isolated mitochondrial organelles. Importantly, the effect on mitochondria was shown to be dependent upon cardiolipin, an anionic phospholipid unique to mitochondria and a well-known key player in mitochondrial apoptosis. Pharmacological modulators of mitochondrial ion channels failed to inhibit CCR. Thus, we propose a generic mechanism of thrilling mitochondria in which soluble amyloid aggregates have the intrinsic capacity to permeabilise mitochondrial membranes, without the need of any other protein. Finally, six small-molecule compounds and black tea extract were tested for their ability to inhibit permeation of mitochondrial membranes by Aβ42, α-syn and tau aggregate complexes. We found that black tea extract and rosmarinic acid were the most potent mito-protectants, and may thus represent important drug leads to alleviate mitochondrial dysfunction in neurodegenerative diseases.
URI: https://www.um.edu.mt/library/oar//handle/123456789/27756
Appears in Collections:Scholarly Works - FacM&SPat
Scholarly Works - FacM&SPB

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