Extract from the Marine Seaweed Padina pavonica 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 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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The Enigma of Amyloid Forming Proteins: Insights From Molecular Simulations

Australian Journal of Chemistry ◽

10.1071/ch19059 ◽

2019 ◽

Vol 72 (8) ◽

pp. 574 ◽

Cited By ~ 2

Author(s):

Nevena Todorova ◽

Irene Yarovsky

Keyword(s):

Amyloid Fibrils ◽

Conformational Dynamics ◽

Computational Modelling ◽

Amyloid Β ◽

Local Environment ◽

Theoretical Modelling ◽

Apolipoprotein C ◽

Amyloidogenic Peptides ◽

Insight Into ◽

Aggregation Phenomena

Molecular level insight into the interplay between protein sequence, structure, and conformational dynamics is crucial for the comprehensive understanding of protein folding, misfolding, and aggregation phenomena that are pertinent to the formation of amyloid fibrils implicated in several degenerative diseases. Computational modelling provides insight into protein behaviour at spatial and temporal resolution still largely outside the reach of experiments. Herein we present an account of our theoretical modelling research conducted in collaboration with several experimental groups where we explored the effects of local environment on the structure and aggregation propensity of several types of amyloidogenic peptides and proteins, including apolipoprotein C-II, insulin, amylin, and amyloid-β using a variety of computational approaches.

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Lipid Inhibitory Effect of (−)-loliolide Isolated from Sargassum horneri in 3T3-L1 Adipocytes: Inhibitory Mechanism of Adipose-Specific Proteins

Marine Drugs ◽

10.3390/md19020096 ◽

2021 ◽

Vol 19 (2) ◽

pp. 96

Author(s):

Hyo-Geun Lee ◽

Hyun-Soo Kim ◽

Jun-Geon Je ◽

Jin Hwang ◽

K. K. Asanka Sanjeewa ◽

...

Keyword(s):

Lipid Accumulation ◽

Binding Protein ◽

Biological Activities ◽

Brown Seaweed ◽

Inhibitory Effect ◽

Sargassum Horneri ◽

Lipid Lowering ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Fatty Acid Binding

Sargassum horneri (S. horneri) is a well-known brown seaweed widely distributed worldwide. Several biological activities of S. horneri have been reported. However, its effects on lipid metabolism and the underlying mechanisms remain elusive. In the present study, we examined the inhibitory effect of the active compound “(−)-loliolide ((6S,7aR)-6-hydroxy-4,4,7a-trimethyl-5,6,7,7a-tetrahydro-1-benzofuran-2(4H)-one (HTT))” from S. horneri extract on lipid accumulation in differentiated adipocytes. MTT assays demonstrated that (−)-loliolide is not toxic to 3T3-L1 adipocytes in a range of concentrations. (−)-loliolide significantly reduced intracellular lipid accumulation in the differentiated phase of 3T3-L1 adipocytes as shown by Oil Red O staining. Western blot analysis revealed that (−)-loliolide increased the expression of lipolytic protein phospho-hormone-sensitive lipase (p-HSL) and thermogenic protein peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1). Additionally, (−)-loliolide decreased expression of adipogenic and lipogenic proteins, including sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), and fatty acid-binding protein 4 (FABP4) in 3T3-L1 adipocytes. These results indicate that (−)-loliolide from S. horneri could suppress lipid accumulation via regulation of antiadipogenic and prolipolytic mechanisms in 3T3-L1 cells. Considering the multifunctional effect of (−)-loliolide, it can be useful as a lipid-lowering agent in the management of patients who suffer from obesity.

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Functionalization of amyloid fibrils via the Bri2 BRICHOS domain

Scientific Reports ◽

10.1038/s41598-020-78732-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Henrik Biverstål ◽

Rakesh Kumar ◽

Anna Katharina Schellhaus ◽

Médoune Sarr ◽

Nico P. Dantuma ◽

...

Keyword(s):

Amyloid Fibrils ◽

Cultured Cells ◽

Cell Attachment ◽

Amyloid Β ◽

Attachment Sites ◽

Human Proteins ◽

Scaffold Materials ◽

Amyloidogenic Peptides ◽

Aβ Fibrils

AbstractAmyloid fibrils are mechanically robust and partly resistant to proteolytic degradation, making them potential candidates for scaffold materials in cell culture, tissue engineering, drug delivery and other applications. Such applications of amyloids would benefit from the possibility to functionalize the fibrils, for example by adding growth factors or cell attachment sites. The BRICHOS domain is found in a family of human proteins that harbor particularly amyloid-prone regions and can reduce aggregation as well as toxicity of several different amyloidogenic peptides. Recombinant human (rh) BRICHOS domains have been shown to bind to the surface of amyloid-β (Aβ) fibrils by immune electron microscopy. Here we produce fusion proteins between mCherry and rh Bri2 BRICHOS and show that they can bind to different amyloid fibrils with retained fluorescence of mCherry in vitro as well as in cultured cells. This suggests a “generic” ability of the BRICHOS domain to bind fibrillar surfaces that can be used to synthesize amyloid decorated with different protein functionalities.

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Rapid formation of peptide/lipid co-aggregates by the amyloidogenic seminal peptide PAP248-286

10.1101/2020.03.04.976746 ◽

2020 ◽

Author(s):

E.W. Vane ◽

S. He ◽

L. Maibaum ◽

A. Nath

Keyword(s):

Acid Phosphatase ◽

Antimicrobial Peptides ◽

Viral Infection ◽

Lipid Membranes ◽

Amyloid Fibrils ◽

Biological Activities ◽

Lipid Vesicles ◽

Prostatic Acid Phosphatase ◽

Distinct Species ◽

Critical Surface

AbstractProtein/lipid co-assembly is an understudied phenomenon that is important to the function of antimicrobial peptides as well as the pathological effects of amyloid. Here we study the co-assembly process of PAP248-286, a seminal peptide that displays both amyloid-forming and antimicrobial activity. PAP248-286 is a fragment of prostatic acid phosphatase and has been reported to form amyloid fibrils, known as semen-derived enhancer of viral infection (SEVI), that enhance the viral infectivity of HIV. We find that in addition to forming amyloid, PAP248-286 much more readily assembles with lipid vesicles into peptide/lipid co-aggregates that resemble amyloid fibrils in some important ways but are a distinct species. The formation of these co-aggregates, which we term “messicles”, is controlled by the peptide:lipid (P:L) ratio and by the lipid composition. The optimal P:L ratio is around 1:10 and at least 70% anionic lipid is required for co-aggregate formation. Once formed, messicles are not disrupted by subsequent changes in P:L ratio. We propose that messicles form through a polyvalent assembly mechanism, where a critical surface density of PAP248-286 on liposomes enables peptide-mediated particle bridging into larger species. Even at ~100-fold lower PAP248-286 concentrations, messicles form at least 10-fold faster than amyloid fibrils. It is therefore possible that, some or all of the biological activities assigned to SEVI, the amyloid form of PAP248-286, could instead be attributed to a PAP248-286/lipid co-aggregate. More broadly speaking, this work provides a potential framework for the discovery and characterization of peptide/lipid co-aggregates by other amyloid-forming proteins and antimicrobial peptides.Statement of SignificancePAP248-286, a fragment of prostatic acid phosphatase, forms amyloid thought to enhances the infectivity of many viruses, including HIV. This amyloid, termed semen-derived enhancer of viral infection (SEVI), has been assigned responsibility for all of PAP248-286’s biological activities, while the monomer is thought to be inactive. However, SEVI formation is quite slow and requires very high concentrations of PAP248-286. Here, we show that PAP248-286 can instead assemble much more rapidly with lipid membranes to form another species, mechanistically and morphologically distinct from both monomer and SEVI amyloid. We have characterized this new species, which could play a role in the biological activities currently ascribed to SEVI. Additionally, our proposed mechanism for peptide/lipid co-assembly could apply to other biologically important systems.

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Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

Current Alzheimer Research ◽

10.2174/1567205014666171128102557 ◽

2018 ◽

Vol 15 (6) ◽

pp. 531-543 ◽

Cited By ~ 4

Author(s):

Dominik Szwajgier ◽

Ewa Baranowska-Wojcik ◽

Kamila Borowiec

Keyword(s):

Phenolic Acids ◽

Ex Vivo ◽

Amyloid Β ◽

Inhibitory Effect ◽

In Vivo Studies ◽

Amyloid Β Peptide ◽

Beneficial Effects ◽

Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

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CLAC binds to amyloid β peptides through the positively charged amino acid cluster within the collagenous domain 1 and inhibits formation of amyloid fibrils. Vol. 280 (2005) 8596–8605

Journal of Biological Chemistry ◽

10.1016/s0021-9258(20)66082-3 ◽

2005 ◽

Vol 280 (15) ◽

pp. 15484

Author(s):

Yoshihide Osada ◽

Tadafumi Hashimoto ◽

Akiko Nishimura ◽

Yuko Matsuo ◽

Tomoko Wakabayashi ◽

...

Keyword(s):

Amino Acid ◽

Amyloid Fibrils ◽

Amyloid Β ◽

Collagenous Domain ◽

Amino Acid Cluster ◽

Positively Charged

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Isolation and Purification of Fucoxanthin from Brown Seaweed Sargassum horneri Using Open ODS Column Chromatography and Ethanol Precipitation

Molecules ◽

10.3390/molecules26133777 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3777

Author(s):

Yuemei Ye ◽

Jingwen Sun ◽

Liting Wang ◽

Junwang Zhu ◽

Wei Cui ◽

...

Keyword(s):

Column Chromatography ◽

Recovery Rate ◽

Biological Activities ◽

Brown Seaweed ◽

Sargassum Horneri ◽

Scale Production ◽

Water Mixture ◽

Isolation And Purification ◽

Ethanol Precipitation ◽

Water Solvent

As an abundant marine xanthophyll, fucoxanthin (FX) exhibits a broad range of biological activities. The preparation of high-purity FX is in great demand, however, most of the available methods require organic solvents which cannot meet the green chemistry standard. In the present study, a simple and efficient purification approach for the purification of FX from the brown seaweed Sargassum horneri was carried out. The FX-rich ethanol extract was isolated by octadecylsilyl (ODS) column chromatography using ethanol–water solvent as a gradient eluent. The overwhelming majority of FX was successfully eluted by the ethanol–water mixture (9:1, v/v), with a recovery rate of 95.36%. A parametric study was performed to optimize the aqueous ethanol precipitation process by investigating the effects on the purity and recovery of FX. Under the optimal conditions, the purity of FX was 91.07%, and the recovery rate was 74.98%. Collectively, the eco-friendly method was cost-efficient for the purification of FX. The developed method provides a potential approach for the large-scale production of fucoxanthin from the brown seaweed Sargassum horneri.

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Among Commercially Available Fruit Juices, Pomegranate Is the Most Effective Inhibitor of PMS-Trypsin Amyloid-Like Fibrils Formation

Natural Product Communications ◽

10.1177/1934578x19859127 ◽

2019 ◽

Vol 14 (6) ◽

pp. 1934578X1985912

Author(s):

Phanindra Babu Kasi ◽

Márta Kotormán

Keyword(s):

Type 2 Diabetes ◽

Amyloid Fibrils ◽

Binding Assay ◽

Inhibitory Effect ◽

Fruit Juices ◽

Pomegranate Juice ◽

Effective Inhibitor ◽

Parkinson’S Diseases ◽

Lateral Sclerosis

The formation of amyloid fibrils is associated with many human illnesses, such as Alzheimer’s, Huntington’s, and Parkinson’s diseases, amyotrophic lateral sclerosis, spongiform encephalitis, type 2 diabetes, and primary and secondary systemic amyloidosis. Nutrition contributes to the prevention of these diseases. The aim of our work was to look for commercially available fruit juices that can inhibit the formation of amyloid fibrils. Of the fruit juices that we examined, that of pomegranate was found to be the most effective inhibitory agent using turbidity measurements and Congo red binding assay. According to our experiments, pomegranate juice reduced the amount of PMS-trypsin amyloid-like fibrils to 3.7% at 5-fold dilution compared with the sample without pomegranate. The inhibitory effect of the pomegranate juice was concentration dependent.

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Effect of guaianolides in the meiosis reinitiation of amphibian oocytes

Zygote ◽

10.1017/s0967199416000265 ◽

2016 ◽

Vol 25 (1) ◽

pp. 10-16 ◽

Cited By ~ 2

Author(s):

J. Zapata-Martínez ◽

G. Sánchez-Toranzo ◽

F. Chaín ◽

C.A.N. Catalán ◽

M.I. Bühler

Keyword(s):

Biological Activities ◽

Wide Spectrum ◽

Sesquiterpene Lactones ◽

Inhibitory Effect ◽

Biological Molecules ◽

Plant Metabolites ◽

Major Mechanism ◽

Bufo Arenarum ◽

Asteraceae Family

SummarySesquiterpene lactones (STLs) are a large and structurally diverse group of plant metabolites generally found in the Asteraceae family. STLs exhibit a wide spectrum of biological activities and it is generally accepted that their major mechanism of action is the alkylation of the thiol groups of biological molecules. The guaianolides is one of various groups of STLs. Anti-tumour and anti-migraine effects, an allergenic agent, an inhibitor of smooth muscle cells and of meristematic cell proliferation are only a few of the most commonly reported activities of STLs. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under stimulus with progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. There are previous records of the inhibitory effect of dehydroleucodin (DhL), a guaianolide lactone, on the progression of meiosis. It has been also shown that DhL and its 11,13-dihydroderivative (2H-DhL; a mixture of epimers at C-11) act as blockers of the resumption of meiosis in fully grown ovarian oocytes from the amphibian Rhinella arenarum (formerly classified as Bufo arenarum). The aim of this study was to analyze the effect of four closely related guaianolides, i.e., DhL, achillin, desacetoxymatricarin and estafietin as possible inhibitors of meiosis in oocytes of amphibians in vitro and discuss some structure–activity relationships. It was found that the inhibitory effect on meiosis resumption is greater when the lactone has two potentially reactive centres, either a α,β–α′,β′-diunsaturated cyclopentanone moiety or an epoxide group plus an exo-methylene-γ-lactone function.

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