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Reducing the assemblies of amyloid-beta multimers by sodium dodecyl sulfate surfactant at concentrations lower than
Hamed Zahraee1,2,3, Fatemeh Mohammadi1,2,3, Elahe Parvaee4
1Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract:
Amyloid-β peptide, the predominant proteinaceous component of senile plaques, is responsible for the incidence of Alzheimer's disease (AD), an age-associated neurodegenerative disorder. Specifically, the amyloid-β(1-42) (Aβ1-42) isoform, known for its high toxicity, is the predominant biomarker for the preliminary diagnosis of AD. The aggregation of the Aβ1-42 peptides can be affected by the components of the cellular medium through changing their structures and molecular interactions. In this study, we investigated the effect of sodium dodecyl sulfate (SDS) at much lower concentrations than the critical micelle concentration (CMC) on Aβ1-42 aggregation. For this purpose, we studied mono-, di-, tri- and tetramers of Aβ1-42 peptide in two different concentrations of SDS molecules (10 and 40 molecules) using a 300 ns molecular dynamics simulation for each system. The distance between the center of mass (COM) of Aβ1-42 peptides confirms that an increase in the number of SDS molecules decreases their aggregation probability due to greater interaction with SDS molecules. Besides, the less compactness parameter reveals the reduced aggregation probability of Aβ1-42 peptides. Based on the energetic FEL landscapes, SDS molecules with the concentration closer to the CMC are an effective inhibitory agent to prevent the formation of Aβ1-42 fibrils. Also, the aggregation direction of the peptide pairs can be predicted by determining the direction of the accumulation-deterrent forces.Communicated by Ramaswamy H. Sarma.
Insights
Sodium dodecyl sulfate (SDS) at low concentrations inhibits amyloid-β(1-42) peptide aggregation, a key factor in Alzheimer's disease (AD). This finding offers potential therapeutic strategies for AD by preventing toxic Aβ1-42 fibril formation.
Area of Science:
- Biochemistry
- Neuroscience
- Computational Biology
Background:
- Alzheimer's disease (AD) is linked to amyloid-β (Aβ) peptide aggregation, particularly the toxic Aβ1-42 isoform.
- Cellular medium components influence Aβ1-42 structure and aggregation.
- Understanding Aβ1-42 interactions is crucial for developing AD therapies.
Purpose of the Study:
- Investigate the effect of low sodium dodecyl sulfate (SDS) concentrations on Aβ1-42 aggregation.
- Determine how SDS influences Aβ1-42 peptide structure and interaction.
- Evaluate SDS as a potential inhibitor of Aβ1-42 fibril formation.
Main Methods:
- Employed molecular dynamics simulations (300 ns) on Aβ1-42 monomers, dimers, trimers, and tetramers.
- Studied Aβ1-42 peptide systems with 10 and 40 SDS molecules.
- Analyzed center of mass distances, compactness parameters, and free energy landscape (FEL) profiles.
Main Results:
- Increased SDS molecules reduced Aβ1-42 aggregation probability due to enhanced peptide-SDS interactions.
- Reduced peptide compactness indicated decreased aggregation propensity.
- SDS concentrations near the critical micelle concentration (CMC) showed significant inhibitory effects on Aβ1-42 fibril formation.
Conclusions:
- Low concentrations of SDS effectively inhibit Aβ1-42 aggregation, suggesting a therapeutic potential for Alzheimer's disease.
- SDS interaction modulates Aβ1-42 peptide structure, preventing the formation of toxic aggregates.
- Predicting aggregation direction through accumulation-deterrent forces offers insights into therapeutic intervention strategies.
