Rotherham, M ORCID: https://orcid.org/0000-0002-9297-7681, Nahar, T, Goodman, T, Telling, ND, Gates, M and El Haj, A (2019) Magnetic Mechanoactivation of Wnt Signaling Augments Dopaminergic Differentiation of Neuronal Cells. Advanced Biosystems, 3 (9). 1900091 - 1900091.

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Abstract

Wnt signaling is a key developmental pathway that regulates dopaminergic progenitor cell proliferation and differentiation during neuronal development. This makes Wnt signaling an important therapeutic target for neurodegenerative conditions such as Parkinson’s disease. Wnt signaling can be modulated using peptides such as UM206, which bind to the Wnt receptor Frizzled.
Previous work has demonstrated remote activation of the Wnt pathway through Frizzled using peptide-functionalized magnetic nanoparticles (MNPs) with magnetic field stimulation. Using this technology, Wnt signaling is remotely activated in the neuronal cell line SH-SY5Y, and the phenotypic response to stimulation is assessed. Results indicate β-catenin translocalization and activation of TCF/LEF responsive transcription in response to MNP and magnetic fields, which result in dopaminergic marker expression when synergistically combined with differentiation factors retinoic acid and the phorbol ester phorbol 12-myristate 13-acetate. This approach is translated into ex vivo postnatal rat brain slices modeling the developing nigrostriatal pathway. Dopaminergic marker expression is maintained in MNP-labeled SH-SY5Y cells after injection and magnetic stimulation. These results demonstrate the translational value of remote control of signal transduction for controlling neuronal precursor cell behavior and highlight the potential applications for controlled cell differentiation as part of cell therapies for neurodegenerative disease.

Item Type: Article
Additional Information: This is the final published version of the article (version of record). It first appeared online via Wiley at https://doi.org/10.1002/adbi.201900091 - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: magnetic nanoparticles; neuronal differentiation; SH‐SY5Y; Wnt signaling
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Symplectic
Date Deposited: 22 Aug 2019 09:21
Last Modified: 22 Sep 2019 16:11
URI: http://eprints.keele.ac.uk/id/eprint/6724

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