Sialylation of chitosan to mitigate Aβ toxicity
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 patholo...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SpringerOpen
2023-02-01
|
| Series: | Bulletin of the National Research Centre |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s42269-023-00990-6 |
| _version_ | 1811166070025748480 |
|---|---|
| author | Dhruva Dhavale Hy K. Lai Paityn Warwick James E. Henry |
| author_facet | Dhruva Dhavale Hy K. Lai Paityn Warwick James E. Henry |
| author_sort | Dhruva Dhavale |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T15:46:32Z |
| format | Article |
| id | doaj.art-8b61287f0e314751a44788d804b63fa5 |
| institution | Directory Open Access Journal |
| issn | 2522-8307 |
| language | English |
| last_indexed | 2024-04-10T15:46:32Z |
| publishDate | 2023-02-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Bulletin of the National Research Centre |
| spelling | doaj.art-8b61287f0e314751a44788d804b63fa52023-02-12T12:03:54ZengSpringerOpenBulletin of the National Research Centre2522-83072023-02-0147111610.1186/s42269-023-00990-6Sialylation of chitosan to mitigate Aβ toxicityDhruva Dhavale0Hy K. Lai1Paityn Warwick2James E. Henry3Cain Department of Chemical Engineering, Louisiana State UniversityDan F. Smith Department of Chemical and Biomolecular Engineering, Lamar UniversityDepartment of Biology, Lamar UniversityDan F. Smith Department of Chemical and Biomolecular Engineering, Lamar UniversityAbstract 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.https://doi.org/10.1186/s42269-023-00990-6Alzheimer’s diseaseAmyloidSialic acidToxicityAggregation |
| spellingShingle | Dhruva Dhavale Hy K. Lai Paityn Warwick James E. Henry Sialylation of chitosan to mitigate Aβ toxicity Bulletin of the National Research Centre Alzheimer’s disease Amyloid Sialic acid Toxicity Aggregation |
| title | Sialylation of chitosan to mitigate Aβ toxicity |
| title_full | Sialylation of chitosan to mitigate Aβ toxicity |
| title_fullStr | Sialylation of chitosan to mitigate Aβ toxicity |
| title_full_unstemmed | Sialylation of chitosan to mitigate Aβ toxicity |
| title_short | Sialylation of chitosan to mitigate Aβ toxicity |
| title_sort | sialylation of chitosan to mitigate aβ toxicity |
| topic | Alzheimer’s disease Amyloid Sialic acid Toxicity Aggregation |
| url | https://doi.org/10.1186/s42269-023-00990-6 |
| work_keys_str_mv | AT dhruvadhavale sialylationofchitosantomitigateabtoxicity AT hyklai sialylationofchitosantomitigateabtoxicity AT paitynwarwick sialylationofchitosantomitigateabtoxicity AT jamesehenry sialylationofchitosantomitigateabtoxicity |