Sialylation of chitosan to mitigate Aβ toxicity

Autor: Dhruva Dhavale, Hy K. Lai, Paityn Warwick, James E. Henry
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Bulletin of the National Research Centre, Vol 47, Iss 1, Pp 1-16 (2023)
Druh dokumentu: article
ISSN: 2522-8307
DOI: 10.1186/s42269-023-00990-6
Popis: Abstract Background Amyloid beta peptide (Aβ) is the main component of plaques and is known to play a role in the development of Alzheimer's disease (AD). As a result, structures that can trap Aβ or disrupt the interaction between Aβ and cells have been researched as a way to lessen the pathological effects of Aβ. Particularly, sialylated compounds that exhibit clustering effects could be advantageous. Results Through the use of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide chemistry, sialic acid (N-acetylneuraminic acid) was used to decorate a chitosan backbone. The compounds were characterized using Fourier-transform infrared spectroscopy (FTIR) and colorimetric assays. Using the model neuroblastoma cell line SH-SY5Y, the ability of these compounds to lessen the toxicity of Aβ was examined in vitro. Successful in vitro mitigation of Aβ toxicity was found to be critically dependent on the degree of sialylation. In particular, a balance between the degree of sialylation and molecular flexibility was determined to be the criteria as it allows for natural clustering. Additionally, chitosan alone demonstrated low levels of cellular toxicity with moderate levels of toxicity mitigation (comparable to low degrees of labelling). Conclusions Compounds were successfully produced, and they varied in their effectiveness in reducing Aβ's toxicity to cells in culture. The effect of molecular flexibility and clustering on toxicity mitigation is explained in this work. This shows the potential of polymeric sugars for the creation of AD treatments.
Databáze: Directory of Open Access Journals
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