Novel tools towards magnetic guidance of neurite growth

  • Parkinson’s disease (PD) is a neurodegenerative disease associated with loss or dysfunction of dopaminergic neurons located in the substantia nigra (SN), and there is no cure available. An emerging new approach for treatment is to transplant human induced dopaminergic neurons directly into the denervated striatal brain target region. Unfortunately, neurons grafted into the substantia nigra are unable to grow axons into the striatum and thus do not allow recovery of the original connectivity. Towards overcoming this general limitation in guided neuronal regeneration, we develop here magnetic nanoparticles functionalized with proteins involved in the regulation of axonal growth. We show covalent binding of constitutive active human rat sarcoma (RAS) proteins or RAS guanine nucleotide exchange factor catalytic domain of son of sevenless (SOS) by fluorescence correlation spectroscopy and multiangle light scattering as well as the characterization of exchange factor activity. Human dopaminergic neurons were differentiated from neural precursor cells and characterized by electrophysiological and immune histochemical methods. Furthermore, we demonstrate magnetic translocation of cytoplasmic \(\gamma-Fe_{2}O_{3}@SiO_{2}\) core-shell nanoparticles into the neurite extensions of induced human neurons. Altogether, we developed tools towards remote control of directed neurite growth in human dopaminergic neurons. These results may have relevance for future therapeutic approaches of cell replacement therapy in Parkinson’s disease.

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Metadaten
Author:Hendrik SchönebornORCiDGND, Fabian RaudzusORCiDGND, Emilie SecretORCiDGND, Nils OttenGND, Aude MichelGND, Jérome FresnaisORCiDGND, Christine MénagerORCiDGND, Jean-Michel SiaugueORCiDGND, Holm ZähresORCiDGND, Irmgard D. Dietzel-MeyerORCiDGND, Rolf HeumannORCiDGND
URN:urn:nbn:de:hbz:294-67646
DOI:https://doi.org/10.3390/jfb10030032
Parent Title (English):Journal of functional biomaterials
Subtitle (English):(I) guidance of magnetic nanoparticles into neurite extensions of induced human neurons and in vitro functionalization with RAS regulating proteins
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2019/11/27
Date of first Publication:2019/07/16
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Open Access Fonds
GTP exchange factor; Parkinson's disease; RAS GTPase; SOS; dopaminergic neuron; fluorescence correlation spectroscopy; magnetic nanoparticle; magnetic nanoparticles; multiangle light scattering; regeneration
Volume:10
Issue:3, Artikel 32
First Page:32-1
Last Page:32-24
Note:
Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum.
Institutes/Facilities:Institut für Anatomie, Abteilung für Anatomie und Molekulare Embryologie
Lehrstuhl Biochemie II, Arbeitsgruppe Molekulare Neurobiochemie
Lehrstuhl Biochemie II, Arbeitsgruppe Elektrobiochemie neuraler Zellen
open_access (DINI-Set):open_access
faculties:Fakultät für Chemie und Biochemie
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International