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Peptides derived from the knuckle epitope of BMP-9 induce the cholinergic differentiation and inactivate GSk3beta in human SH-SY5Y neuroblastoma cells

Marc-Antoine Lauzon, Olivier Drevelle and Nathalie Faucheux

Article (2017)

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Cite this document: Lauzon, M.-A., Drevelle, O. & Faucheux, N. (2017). Peptides derived from the knuckle epitope of BMP-9 induce the cholinergic differentiation and inactivate GSk3beta in human SH-SY5Y neuroblastoma cells. Scientific Reports, 7. doi:10.1038/s41598-017-04835-x
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Abstract

The incidence of brain degenerative disorders like Alzheimer's disease (AD) will increase as the world population ages. While there is presently no known cure for AD and current treatments having only a transient effect, an increasing number of publications indicate that growth factors (GF) may be used to treat AD. GFs like the bone morphogenetic proteins (BMPs), especially BMP-9, affect many aspects of AD. However, BMP-9 is a big protein that cannot readily cross the blood-brain barrier. We have therefore studied the effects of two small peptides derived from BMP-9 (pBMP-9 and SpBMP-9). We investigated their capacity to differentiate SH-SY5Y human neuroblastoma cells into neurons with or without retinoic acid (RA). Both peptides induced Smad 1/5 phosphorylation and their nuclear translocation. They increased the number and length of neurites and the expression of neuronal markers MAP-2, NeuN and NSE better than did BMP-9. They also promoted differentiation to the cholinergic phenotype more actively than BMP-9, SpBMP-9 being the most effective as shown by increases in intracellular acetylcholine, ChAT and VAchT. Finally, both peptides activated the PI3K/Akt pathway and inhibited GSK3beta, a current AD therapeutic target. BMP-9-derived peptides, especially SpBMP-9, with or without RA, are promising molecules that warrant further investigation.

Uncontrolled Keywords

Alzheimer Disease/*metabolism; Binding Sites; Cell Differentiation/drug effects; Cell Line, Tumor; Down-Regulation; Gene Expression Regulation/drug effects; Glycogen Synthase Kinase 3 beta/*metabolism; Growth Differentiation Factors/*chemistry/metabolism; Humans; Models, Biological; Neuroblastoma/*metabolism; Neurons/*cytology/drug effects/metabolism; Peptides/chemistry/*pharmacology; Signal Transduction/drug effects; Tretinoin/pharmacology

Open Access document in PolyPublie
Subjects: 1800 Génie chimique > 1800 Génie chimique
1900 Génie biomédical > 1900 Génie biomédical
Department: Département de génie chimique
Research Center: Non applicable
Funders: CRSNG/NSERC
Grant number: 298359
Date Deposited: 17 Dec 2021 10:59
Last Modified: 28 Mar 2022 12:51
PolyPublie URL: https://publications.polymtl.ca/4988/
Document issued by the official publisher
Journal Title: Scientific Reports (vol. 7)
Publisher: Nature
Official URL: https://doi.org/10.1038/s41598-017-04835-x

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