Sustained CREB phosphorylation by lipid-peptide liquid crystalline nanoassemblies
Abstract Cyclic-AMP-response element-binding protein (CREB) is a leucine zipper class transcription factor that is activated through phosphorylation. Ample CREB phosphorylation is required for neurotrophin expression, which is of key importance for preventing and regenerating neurological disorders,...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-023-01043-9 |
| _version_ | 1797630362468220928 |
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| author | Yu Wu Borislav Angelov Yuru Deng Takehiko Fujino Md Shamim Hossain Markus Drechsler Angelina Angelova |
| author_facet | Yu Wu Borislav Angelov Yuru Deng Takehiko Fujino Md Shamim Hossain Markus Drechsler Angelina Angelova |
| author_sort | Yu Wu |
| collection | DOAJ |
| description | Abstract Cyclic-AMP-response element-binding protein (CREB) is a leucine zipper class transcription factor that is activated through phosphorylation. Ample CREB phosphorylation is required for neurotrophin expression, which is of key importance for preventing and regenerating neurological disorders, including the sequelae of long COVID syndrome. Here we created lipid-peptide nanoassemblies with different liquid crystalline structural organizations (cubosomes, hexosomes, and vesicles) as innovative nanomedicine delivery systems of bioactive PUFA-plasmalogens (vinyl ether phospholipids with polyunsaturated fatty acid chains) and a neurotrophic pituitary adenylate cyclase-activating polypeptide (PACAP). Considering that plasmalogen deficiency is a potentially causative factor for neurodegeneration, we examined the impact of nanoassemblies type and incubation time in an in vitro Parkinson’s disease (PD) model as critical parameters for the induction of CREB phosphorylation. The determined kinetic changes in CREB, AKT, and ERK-protein phosphorylation reveal that non-lamellar PUFA-plasmalogen-loaded liquid crystalline lipid nanoparticles significantly prolong CREB activation in the neurodegeneration model, an effect unattainable with free drugs, and this effect can be further enhanced by the cell-penetrating peptide PACAP. Understanding the sustained CREB activation response to neurotrophic nanoassemblies might lead to more efficient use of nanomedicines in neuroregeneration. |
| first_indexed | 2024-03-11T11:07:18Z |
| format | Article |
| id | doaj.art-33017c9842b541c7b428e29307969fae |
| institution | Directory Open Access Journal |
| issn | 2399-3669 |
| language | English |
| last_indexed | 2024-03-11T11:07:18Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj.art-33017c9842b541c7b428e29307969fae2023-11-12T12:09:28ZengNature PortfolioCommunications Chemistry2399-36692023-11-016111610.1038/s42004-023-01043-9Sustained CREB phosphorylation by lipid-peptide liquid crystalline nanoassembliesYu Wu0Borislav Angelov1Yuru Deng2Takehiko Fujino3Md Shamim Hossain4Markus Drechsler5Angelina Angelova6Université Paris-Saclay, CNRS, Institut Galien Paris-SaclayExtreme Light Infrastructure ERICWenzhou Institute, University of Chinese Academy of SciencesInstitute of Rheological Functions of FoodInstitute of Rheological Functions of FoodKeylab “Electron and Optical Microscopy”, Bavarian Polymerinstitute (BPI), University of BayreuthUniversité Paris-Saclay, CNRS, Institut Galien Paris-SaclayAbstract Cyclic-AMP-response element-binding protein (CREB) is a leucine zipper class transcription factor that is activated through phosphorylation. Ample CREB phosphorylation is required for neurotrophin expression, which is of key importance for preventing and regenerating neurological disorders, including the sequelae of long COVID syndrome. Here we created lipid-peptide nanoassemblies with different liquid crystalline structural organizations (cubosomes, hexosomes, and vesicles) as innovative nanomedicine delivery systems of bioactive PUFA-plasmalogens (vinyl ether phospholipids with polyunsaturated fatty acid chains) and a neurotrophic pituitary adenylate cyclase-activating polypeptide (PACAP). Considering that plasmalogen deficiency is a potentially causative factor for neurodegeneration, we examined the impact of nanoassemblies type and incubation time in an in vitro Parkinson’s disease (PD) model as critical parameters for the induction of CREB phosphorylation. The determined kinetic changes in CREB, AKT, and ERK-protein phosphorylation reveal that non-lamellar PUFA-plasmalogen-loaded liquid crystalline lipid nanoparticles significantly prolong CREB activation in the neurodegeneration model, an effect unattainable with free drugs, and this effect can be further enhanced by the cell-penetrating peptide PACAP. Understanding the sustained CREB activation response to neurotrophic nanoassemblies might lead to more efficient use of nanomedicines in neuroregeneration.https://doi.org/10.1038/s42004-023-01043-9 |
| spellingShingle | Yu Wu Borislav Angelov Yuru Deng Takehiko Fujino Md Shamim Hossain Markus Drechsler Angelina Angelova Sustained CREB phosphorylation by lipid-peptide liquid crystalline nanoassemblies Communications Chemistry |
| title | Sustained CREB phosphorylation by lipid-peptide liquid crystalline nanoassemblies |
| title_full | Sustained CREB phosphorylation by lipid-peptide liquid crystalline nanoassemblies |
| title_fullStr | Sustained CREB phosphorylation by lipid-peptide liquid crystalline nanoassemblies |
| title_full_unstemmed | Sustained CREB phosphorylation by lipid-peptide liquid crystalline nanoassemblies |
| title_short | Sustained CREB phosphorylation by lipid-peptide liquid crystalline nanoassemblies |
| title_sort | sustained creb phosphorylation by lipid peptide liquid crystalline nanoassemblies |
| url | https://doi.org/10.1038/s42004-023-01043-9 |
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