Extract from the Marine Seaweed Padina pavonica Protects Mitochondrial Biomembranes from Damage by Amyloidogenic Peptides |
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Authors: | Mario Caruana Angelique Camilleri Maria Ylenia Farrugia Stephanie Ghio Michaela Jakubí
kov Ruben J Cauchi Neville Vassallo |
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Institution: | 1.Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, 2023 Msida, Malta; (M.C.); (A.C.); (M.Y.F.); (S.G.); (M.J.); (R.J.C.);2.Centre for Molecular Medicine and Biobanking, Biomedical Sciences Building, University of Malta, 2023 Msida, Malta;3.Department of Experimental Biology, Faculty of Science, Masaryk University, 60300 Brno, Czech Republic |
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Abstract: | The identification of compounds which protect the double-membrane of mitochondrial organelles from disruption by toxic confomers of amyloid proteins may offer a therapeutic strategy to combat human neurodegenerative diseases. Here, we exploited an extract from the marine brown seaweed Padina pavonica (PPE) as a vital source of natural bioactive compounds to protect mitochondrial membranes against insult by oligomeric aggregates of the amyloidogenic proteins amyloid-β (Aβ), α-synuclein (α-syn) and tau, which are currently considered to be major targets for drug discovery in Alzheimer’s disease (AD) and Parkinson’s disease (PD). We show that PPE manifested a significant inhibitory effect against swelling of isolated mitochondria exposed to the amyloid oligomers, and attenuated the release of cytochrome c from the mitochondria. Using cardiolipin-enriched synthetic lipid membranes, we also show that dye leakage from fluorophore-loaded vesicles and formation of channel-like pores in planar bilayer membranes are largely prevented by incubating the oligomeric aggregates with PPE. Lastly, we demonstrate that PPE curtails the ability of Aβ42 and α-syn monomers to self-assemble into larger β-aggregate structures, as well as potently disrupts their respective amyloid fibrils. In conclusion, the mito-protective and anti-aggregator biological activities of Padina pavonica extract may be of therapeutic value in neurodegenerative proteinopathies, such as AD and PD. |
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Keywords: | Padina pavonica seaweed extract Alzheimer’ s disease Parkinson’ s disease mitochondria amyloidogenic proteins membrane permeabilization |
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