| Title: |
Cyclic undecapeptide Cyclosporin A mediated inhibition of amyloid synthesis: Implications in alleviation of amyloid induced neurotoxicity |
| Authors: |
Kazmi, Shadab; Mujeeb, Anzar Abdul; Owais, Mohammad |
| Source: |
Scientific Reports ; volume 8, issue 1 ; ISSN 2045-2322 |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2018 |
| 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41598-018-35645-4 |
| Availability: |
http://dx.doi.org/10.1038/s41598-018-35645-4; https://www.nature.com/articles/s41598-018-35645-4.pdf; https://www.nature.com/articles/s41598-018-35645-4 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| Accession Number: |
edsbas.4F50120F |
| Database: |
BASE |