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Ligand Nano-cluster Arrays in a Supported Lipid Bilayer
Published on: April 23, 2017
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Sustained CREB phosphorylation by lipid-peptide liquid crystalline nanoassemblies
Yu Wu1, Borislav Angelov2, Yuru Deng3
1Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, F-91400, Orsay, France.
Communications Chemistry
|November 6, 2023
Summary
Novel lipid-peptide nanoassemblies effectively deliver polyunsaturated fatty acid-plasmalogens and pituitary adenylate cyclase-activating polypeptide (PACAP) to prolong cyclic-AMP-response element-binding protein (CREB) activation in a Parkinson
Area of Science:
- Neuroscience
- Nanomedicine
- Biochemistry
Background:
- Cyclic-AMP-response element-binding protein (CREB) phosphorylation is crucial for neurotrophin expression and neurological disorder treatment.
- Plasmalogen deficiency is linked to neurodegeneration, highlighting the need for effective delivery systems.
- Long COVID syndrome and Parkinson's disease (PD) involve neurodegenerative processes where CREB activation is beneficial.
Purpose of the Study:
- To develop and evaluate lipid-peptide nanoassemblies for delivering polyunsaturated fatty acid-plasmalogens and pituitary adenylate cyclase-activating polypeptide (PACAP).
- To investigate the impact of different nanoassembly structures and incubation times on CREB phosphorylation in an in vitro PD model.
- To assess the potential of these nanomedicines for neuroregeneration by studying sustained CREB activation.
Main Methods:
- Creation of lipid-peptide nanoassemblies with varying liquid crystalline structures (cubosomes, hexosomes, vesicles).
- Incorporation of bioactive PUFA-plasmalogens and the neurotrophic peptide PACAP into the nanoassemblies.
- Assessment of CREB, AKT, and ERK protein phosphorylation kinetics in an in vitro Parkinson's disease model.
Main Results:
- Non-lamellar, PUFA-plasmalogen-loaded liquid crystalline lipid nanoparticles significantly prolonged CREB activation compared to free drugs.
- The cell-penetrating peptide PACAP further enhanced the sustained CREB activation effect.
- Different nanoassembly structures and incubation times influenced the phosphorylation kinetics.
Conclusions:
- Lipid-peptide nanoassemblies represent a promising nanomedicine strategy for delivering neurotrophic agents.
- Sustained CREB activation achieved through these nanoassemblies offers a potential therapeutic avenue for neurodegenerative diseases.
- Understanding the sustained CREB activation response can optimize the use of nanomedicines in neuroregeneration.
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