Extract from the Marine Seaweed <i>Padina pavonica</i> Protects Mitochondrial Biomembranes from Damage by Amyloidogenic Peptides
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 <i>Padin...
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MDPI AG
2021-03-01
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author | Mario Caruana Angelique Camilleri Maria Ylenia Farrugia Stephanie Ghio Michaela Jakubíčková Ruben J. Cauchi Neville Vassallo |
author_facet | Mario Caruana Angelique Camilleri Maria Ylenia Farrugia Stephanie Ghio Michaela Jakubíčková Ruben J. Cauchi Neville Vassallo |
author_sort | Mario Caruana |
collection | DOAJ |
description | 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 <i>Padina pavonica</i> (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 <i>c</i> 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 <i>Padina pavonica</i> extract may be of therapeutic value in neurodegenerative proteinopathies, such as AD and PD. |
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issn | 1420-3049 |
language | English |
last_indexed | 2024-03-09T05:06:46Z |
publishDate | 2021-03-01 |
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series | Molecules |
spelling | doaj.art-2c5a4fb5ff9b4b7b932d8ad13f24f47b2023-12-03T12:53:25ZengMDPI AGMolecules1420-30492021-03-01265144410.3390/molecules26051444Extract from the Marine Seaweed <i>Padina pavonica</i> Protects Mitochondrial Biomembranes from Damage by Amyloidogenic PeptidesMario Caruana0Angelique Camilleri1Maria Ylenia Farrugia2Stephanie Ghio3Michaela Jakubíčková4Ruben J. Cauchi5Neville Vassallo6Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, 2023 Msida, MaltaDepartment of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, 2023 Msida, MaltaDepartment of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, 2023 Msida, MaltaDepartment of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, 2023 Msida, MaltaDepartment of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, 2023 Msida, MaltaDepartment of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, 2023 Msida, MaltaDepartment of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, 2023 Msida, MaltaThe 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 <i>Padina pavonica</i> (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 <i>c</i> 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 <i>Padina pavonica</i> extract may be of therapeutic value in neurodegenerative proteinopathies, such as AD and PD.https://www.mdpi.com/1420-3049/26/5/1444<i>Padina pavonica</i> seaweed extractAlzheimer’s diseaseParkinson’s diseasemitochondriaamyloidogenic proteinsmembrane permeabilization |
spellingShingle | Mario Caruana Angelique Camilleri Maria Ylenia Farrugia Stephanie Ghio Michaela Jakubíčková Ruben J. Cauchi Neville Vassallo Extract from the Marine Seaweed <i>Padina pavonica</i> Protects Mitochondrial Biomembranes from Damage by Amyloidogenic Peptides Molecules <i>Padina pavonica</i> seaweed extract Alzheimer’s disease Parkinson’s disease mitochondria amyloidogenic proteins membrane permeabilization |
title | Extract from the Marine Seaweed <i>Padina pavonica</i> Protects Mitochondrial Biomembranes from Damage by Amyloidogenic Peptides |
title_full | Extract from the Marine Seaweed <i>Padina pavonica</i> Protects Mitochondrial Biomembranes from Damage by Amyloidogenic Peptides |
title_fullStr | Extract from the Marine Seaweed <i>Padina pavonica</i> Protects Mitochondrial Biomembranes from Damage by Amyloidogenic Peptides |
title_full_unstemmed | Extract from the Marine Seaweed <i>Padina pavonica</i> Protects Mitochondrial Biomembranes from Damage by Amyloidogenic Peptides |
title_short | Extract from the Marine Seaweed <i>Padina pavonica</i> Protects Mitochondrial Biomembranes from Damage by Amyloidogenic Peptides |
title_sort | extract from the marine seaweed i padina pavonica i protects mitochondrial biomembranes from damage by amyloidogenic peptides |
topic | <i>Padina pavonica</i> seaweed extract Alzheimer’s disease Parkinson’s disease mitochondria amyloidogenic proteins membrane permeabilization |
url | https://www.mdpi.com/1420-3049/26/5/1444 |
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