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Cyclic undecapeptide Cyclosporin A mediated inhibition of amyloid synthesis: Implications in alleviation of amyloid induced neurotoxicity
Amyloids are highly organized fibril aggregates arise from inappropriately folded form of the protein or polypeptide precursors under both physiological as well as simulated ambience. Amyloid synthesis is a multistep process that involves formation of several metastable intermediates. Among various...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251898/ https://www.ncbi.nlm.nih.gov/pubmed/30470780 http://dx.doi.org/10.1038/s41598-018-35645-4 |
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author | Kazmi, Shadab Mujeeb, Anzar Abdul Owais, Mohammad |
author_facet | Kazmi, Shadab Mujeeb, Anzar Abdul Owais, Mohammad |
author_sort | Kazmi, Shadab |
collection | PubMed |
description | Amyloids are highly organized fibril aggregates arise from inappropriately folded form of the protein or polypeptide precursors under both physiological as well as simulated ambience. Amyloid synthesis is a multistep process that involves formation of several metastable intermediates. Among various intermediate species, the as-formed soluble oligomers are extremely toxic to the neuronal cells. In the present study, we evaluated cyclosporine A (CsA), an undecapeptide, for its potential to prevent aggregation of model protein ovalbumin (OVA). In an attempt to elucidate involved operative mechanism, the preliminary studies delineate that CsA affects both primary nucleation as well as other secondary pathways involved in OVA fibrillation process. By its specific interaction with amyloid intermediates, the cyclic peptide CsA seems to regulate the lag phase of the fibrillation process in concentration dependent manner. The present study further suggests that exposure to CsA during lag phase ensues in reversal of OVA fibrillation process. On the contrary, mature OVA fibril remained impervious to the CsA treatment. The cyclic undecapeptide CsA was also found to successfully alleviate amyloid induced toxicity in neuroblastoma cells. |
format | Online Article Text |
id | pubmed-6251898 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62518982018-11-29 Cyclic undecapeptide Cyclosporin A mediated inhibition of amyloid synthesis: Implications in alleviation of amyloid induced neurotoxicity Kazmi, Shadab Mujeeb, Anzar Abdul Owais, Mohammad Sci Rep Article Amyloids are highly organized fibril aggregates arise from inappropriately folded form of the protein or polypeptide precursors under both physiological as well as simulated ambience. Amyloid synthesis is a multistep process that involves formation of several metastable intermediates. Among various intermediate species, the as-formed soluble oligomers are extremely toxic to the neuronal cells. In the present study, we evaluated cyclosporine A (CsA), an undecapeptide, for its potential to prevent aggregation of model protein ovalbumin (OVA). In an attempt to elucidate involved operative mechanism, the preliminary studies delineate that CsA affects both primary nucleation as well as other secondary pathways involved in OVA fibrillation process. By its specific interaction with amyloid intermediates, the cyclic peptide CsA seems to regulate the lag phase of the fibrillation process in concentration dependent manner. The present study further suggests that exposure to CsA during lag phase ensues in reversal of OVA fibrillation process. On the contrary, mature OVA fibril remained impervious to the CsA treatment. The cyclic undecapeptide CsA was also found to successfully alleviate amyloid induced toxicity in neuroblastoma cells. Nature Publishing Group UK 2018-11-23 /pmc/articles/PMC6251898/ /pubmed/30470780 http://dx.doi.org/10.1038/s41598-018-35645-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Kazmi, Shadab Mujeeb, Anzar Abdul Owais, Mohammad Cyclic undecapeptide Cyclosporin A mediated inhibition of amyloid synthesis: Implications in alleviation of amyloid induced neurotoxicity |
title | Cyclic undecapeptide Cyclosporin A mediated inhibition of amyloid synthesis: Implications in alleviation of amyloid induced neurotoxicity |
title_full | Cyclic undecapeptide Cyclosporin A mediated inhibition of amyloid synthesis: Implications in alleviation of amyloid induced neurotoxicity |
title_fullStr | Cyclic undecapeptide Cyclosporin A mediated inhibition of amyloid synthesis: Implications in alleviation of amyloid induced neurotoxicity |
title_full_unstemmed | Cyclic undecapeptide Cyclosporin A mediated inhibition of amyloid synthesis: Implications in alleviation of amyloid induced neurotoxicity |
title_short | Cyclic undecapeptide Cyclosporin A mediated inhibition of amyloid synthesis: Implications in alleviation of amyloid induced neurotoxicity |
title_sort | cyclic undecapeptide cyclosporin a mediated inhibition of amyloid synthesis: implications in alleviation of amyloid induced neurotoxicity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251898/ https://www.ncbi.nlm.nih.gov/pubmed/30470780 http://dx.doi.org/10.1038/s41598-018-35645-4 |
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