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Trehalose and Magnesium Chloride Exert a Common Anti-amyloidogenic Effect Towards Hen Egg White Lysozyme

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Abstract

Many degenerative disorder such as Parkinsons, Alzheimers, Huntingtons disease, etc are caused due to the deposition of amyloid fibrils, formed due to the ordered aggregation of misfolded/unfolded proteins. Misfolded or unfolded proteins aggregate mostly through hydrophobic interactions which are unexposed in native state, but become exposed upon unfolding. To counteract amyloid related diseases, inhibition of the protein self assembly into fibril is a potential therapeutic strategy. The study aims at investigating the effect of selected compounds, namely trehalose and magnesium chloride hexahydrate towards inhibition and disaggregation of amyloid fibrils using Hen Egg White Lysozyme as a model. We further attempted to understand the mechanism of action with the help of various biophysical, microscopic as well as computational studies. A common mechanism of action was identified where the selected compounds exert their anti-amyloidogenic effects by altering HEWL conformations characterized by reduction in the beta sheet content and decrease in exposed hydrophobic surfaces. The altered conformation seems to have lesser amyloidogenic propensity leading to inhibition as well as disaggregation of amyloids.

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Abbreviations

ANS:

1-Anilinonaphthalene-8-sulphonic acid

BSA:

Bovine serum albumin

CD:

Circular dichroism

DDI:

Distilled deionised

HEWL:

Hen egg white lysozyme

PDB:

Protein data bank

PTA:

Phosphotungstic acid

TEM:

Transmission electron microscope

ThT:

Thioflavin T

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Acknowledgements

The authors acknowledge the infrastructural facilities at NIT Rourkela. The fellowship provided to VK from DBT is also acknowledged.

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Authors and Affiliations

  1. Department of Biotechnology and Medical Engineering, National Institute of Technology Rourkela, Rourkela, Odisha, 769008, India

    Rupsa Chatterjee, Vidyalatha Kolli & Nandini Sarkar

Authors
  1. Rupsa Chatterjee
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  2. Vidyalatha Kolli
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  3. Nandini Sarkar
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Correspondence to Nandini Sarkar.

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The authors declare that they have no conflicts of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Chemical compounds studied in this article—Trehalose (PubChem CID:7427); Magnesium chloride hexahydrate (PubChem CID:24644)

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Chatterjee, R., Kolli, V. & Sarkar, N. Trehalose and Magnesium Chloride Exert a Common Anti-amyloidogenic Effect Towards Hen Egg White Lysozyme. Protein J 36, 138–146 (2017). https://doi.org/10.1007/s10930-017-9705-2

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  • DOI: https://doi.org/10.1007/s10930-017-9705-2

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