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Cell-Penetrating Peptides with Unexpected Anti-Amyloid Properties
Cell-penetrating peptides (CPPs) with sequences derived originally from a prion protein (PrP) have been shown to exhibit both anti-prion and anti-amyloid properties particularly against prion proteins and the amyloid-β (Aβ) peptide active in Alzheimer’s disease. These disease-modifying properties ar...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027922/ https://www.ncbi.nlm.nih.gov/pubmed/35456657 http://dx.doi.org/10.3390/pharmaceutics14040823 |
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author | Österlund, Nicklas Wärmländer, Sebastian K. T. S. Gräslund, Astrid |
author_facet | Österlund, Nicklas Wärmländer, Sebastian K. T. S. Gräslund, Astrid |
author_sort | Österlund, Nicklas |
collection | PubMed |
description | Cell-penetrating peptides (CPPs) with sequences derived originally from a prion protein (PrP) have been shown to exhibit both anti-prion and anti-amyloid properties particularly against prion proteins and the amyloid-β (Aβ) peptide active in Alzheimer’s disease. These disease-modifying properties are so far observed in cell cultures and in vitro. The CPP sequences are composed of a hydrophobic signal sequence followed by a highly positively charged hexapeptide segment. The original signal sequence of the prion protein can be changed to the signal sequence of the NCAM1 protein without losing the anti-prion activity. Although the detailed molecular mechanisms of these CPP peptides are not fully understood, they do form amyloid aggregates by themselves, and molecular interactions between the CPPs and PrP/Aβ can be observed in vitro using various spectroscopic techniques. These initial intermolecular interactions appear to re-direct the aggregation pathways for prion/amyloid formation to less cell-toxic molecular structures (i.e., co-aggregates), which likely is why the disease-inducing PrP/Aβ aggregation is counteracted in vivo. |
format | Online Article Text |
id | pubmed-9027922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90279222022-04-23 Cell-Penetrating Peptides with Unexpected Anti-Amyloid Properties Österlund, Nicklas Wärmländer, Sebastian K. T. S. Gräslund, Astrid Pharmaceutics Review Cell-penetrating peptides (CPPs) with sequences derived originally from a prion protein (PrP) have been shown to exhibit both anti-prion and anti-amyloid properties particularly against prion proteins and the amyloid-β (Aβ) peptide active in Alzheimer’s disease. These disease-modifying properties are so far observed in cell cultures and in vitro. The CPP sequences are composed of a hydrophobic signal sequence followed by a highly positively charged hexapeptide segment. The original signal sequence of the prion protein can be changed to the signal sequence of the NCAM1 protein without losing the anti-prion activity. Although the detailed molecular mechanisms of these CPP peptides are not fully understood, they do form amyloid aggregates by themselves, and molecular interactions between the CPPs and PrP/Aβ can be observed in vitro using various spectroscopic techniques. These initial intermolecular interactions appear to re-direct the aggregation pathways for prion/amyloid formation to less cell-toxic molecular structures (i.e., co-aggregates), which likely is why the disease-inducing PrP/Aβ aggregation is counteracted in vivo. MDPI 2022-04-09 /pmc/articles/PMC9027922/ /pubmed/35456657 http://dx.doi.org/10.3390/pharmaceutics14040823 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Österlund, Nicklas Wärmländer, Sebastian K. T. S. Gräslund, Astrid Cell-Penetrating Peptides with Unexpected Anti-Amyloid Properties |
title | Cell-Penetrating Peptides with Unexpected Anti-Amyloid Properties |
title_full | Cell-Penetrating Peptides with Unexpected Anti-Amyloid Properties |
title_fullStr | Cell-Penetrating Peptides with Unexpected Anti-Amyloid Properties |
title_full_unstemmed | Cell-Penetrating Peptides with Unexpected Anti-Amyloid Properties |
title_short | Cell-Penetrating Peptides with Unexpected Anti-Amyloid Properties |
title_sort | cell-penetrating peptides with unexpected anti-amyloid properties |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027922/ https://www.ncbi.nlm.nih.gov/pubmed/35456657 http://dx.doi.org/10.3390/pharmaceutics14040823 |
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