Charged surfactants induce a non‐fibrillar aggregation pathway of amyloid‐beta peptide

Loureiro, Joana A.; Rocha, Sandra; Pereira, Maria do Carmo

doi:10.1002/psc.2535

Cited by 23 publications

(17 citation statements)

References 38 publications

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“…For the zwitterionic LPC, we propose that it stimulates RPT aggregation similarly to the reported case for the non-charged surfactant OG and Aβ [45, 46]. The presence of amphipathic LPC molecules would promote the exposure of hydrophobic parts of RPT monomers in solution [47–49], thereby facilitating oligomerization and initiating fibril formation.…”

Section: Resultsmentioning

confidence: 78%

Lysophospholipid-Containing Membranes Modulate the Fibril Formation of the Repeat Domain of a Human Functional Amyloid, Pmel17

Jiang

Lee

2014

Journal of Molecular Biology

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Pmel17 is an important protein for pigmentation in human skin and eyes. Proteolytic fragments from Pmel17 form fibrils upon which melanin is deposited in melanosomes. The repeat domain (RPT) derived from Pmel17 only forms fibrils under acidic melanosomal conditions. Here, we examined the effects of lipids on RPT aggregation to explore whether intramelanosomal vesicles can facilitate fibrillogenesis. Using transmission electron microscopy, circular dichroism, and fluorescence spectroscopy, fibril formation was monitored at the ultrastructural, secondary conformational and local level, respectively. Phospholipid vesicles and lysophospholipid (lysolipid) micelles were employed as membrane mimics. The surfactant-like lysolipids are particularly pertinent due to their high content in melanosomal membranes. Interestingly, RPT aggregation kinetics were influenced only by lysolipid-containing phospholipid vesicles. While both vesicles containing either anionic lysophosphatidylglycerol (LPG) or zwitterionic lysophosphatidylcholine (LPC) stimulate aggregation, LPG exerted a greater effect on reducing the apparent nucleation time. A detailed comparison showed distinct behaviors of LPG versus LPC monomers and micelles plausibly originating from their headgroup hydrogen bonding capabilities. Acceleration and retardation of aggregation were observed for LPG monomers and micelles, respectively. Because a specific interaction between LPG and RPT was identified by intrinsic W423 fluorescence and induced α-helical structure, it is inferred that binding of LPG near the C-terminal amyloid core initiates intermolecular association, whereas stabilization of α-helical conformation inhibits β-sheet formation. Contrastingly, LPC promotes RPT aggregation at both submicellar and micellar concentrations via non-specific binding with undetectable secondary structural change. Our findings suggest that protein-lysolipid interactions within melanosomes may regulate amyloid formation in vivo.

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Section: Resultsmentioning

confidence: 78%

Lysophospholipid-Containing Membranes Modulate the Fibril Formation of the Repeat Domain of a Human Functional Amyloid, Pmel17

Jiang

Lee

2014

Journal of Molecular Biology

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“…One possible approach to prevent this process could be the reconversion of the Aβ conformation [ 10 , 11 , 12 ]. Such methodology can be promoted by the addition of a compound capable to remove the beta conformation out of the equilibrium [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol and Grape Extract-loaded Solid Lipid Nanoparticles for the Treatment of Alzheimer’s Disease

et al. 2017

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The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer’s disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to its neuroprotective characteristics. Here, we provide evidence that grape skin and grape seed extracts increase the inhibition effect on Aβ aggregation. However, after intravenous injection, resveratrol is rapidly metabolized into both glucuronic acid and sulfate conjugations of the phenolic groups in the liver and intestinal epithelial cells (within less than 2 h), which are then eliminated. In the present study, we show that solid lipid nanoparticles (SLNs) functionalized with an antibody, the anti-transferrin receptor monoclonal antibody (OX26 mAb), can work as a possible carrier to transport the extract to target the brain. Experiments on human brain-like endothelial cells show that the cellular uptake of the OX26 SLNs is substantially more efficient than that of normal SLNs and SLNs functionalized with an unspecific antibody. As a consequence, the transcytosis ability of these different SLNs is higher when functionalized with OX-26.

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“…The aggregation process is sensitive to pH, temperature, and ionic strength as well as additives such as proteins, 10 − 13 nanoparticles, 14 − 16 and surfactants. 17 Proteins generally retard aggregation whereas diverse effects have been seen for nanoparticles. Retarding effects of proteins have been seen for biologically relevant proteins that interact with Aβ in vivo but also for completely unrelated proteins.…”

Section: Introductionmentioning

confidence: 99%

Effects of Polyamino Acids and Polyelectrolytes on Amyloid β Fibril Formation

2014

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The fibril formation of the neurodegenerative peptide amyloid β (Aβ42) is sensitive to solution conditions, and several proteins and peptides have been found to retard the process. Aβ42 fibril formation was followed with ThT fluorescence in the presence of polyamino acids (poly-glutamic acid, poly-lysine, and poly-threonine) and other polymers (poly(acrylic acid), poly(ethylenimine), and poly(diallyldimethylammonium chloride). An accelerating effect on the Aβ42 aggregation process is observed from all positively charged polymers, while no effect is seen from the negative or neutral polymers. The accelerating effect is dependent on the concentration of positive polymer in a highly reproducible manner. Acceleration is observed from a 1:500 polymer to Aβ42 weight ratio and up. Polyamino acids and the other polymers exert quantitatively the same effect at the same concentrations based on weight. Fibrils are formed in all cases as verified by transmission electron microscopy. The concentrations of polymers required for acceleration are too low to affect the Aβ42 aggregation process through increased ionic strength or molecular crowding effects. Instead, the acceleration seems to arise from the locally increased Aβ42 concentration near the polymers, which favors association and affects the electrostatic environment of the peptide.

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Charged surfactants induce a non‐fibrillar aggregation pathway of amyloid‐beta peptide

Cited by 23 publications

References 38 publications

Lysophospholipid-Containing Membranes Modulate the Fibril Formation of the Repeat Domain of a Human Functional Amyloid, Pmel17

Lysophospholipid-Containing Membranes Modulate the Fibril Formation of the Repeat Domain of a Human Functional Amyloid, Pmel17

Resveratrol and Grape Extract-loaded Solid Lipid Nanoparticles for the Treatment of Alzheimer’s Disease

Effects of Polyamino Acids and Polyelectrolytes on Amyloid β Fibril Formation

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