Perspectives of RAS and RHEB GTPase signaling pathways in regenerating brain neurons
- Cellular activation of RAS GTPases into the GTP-binding “ON” state is a key switch for regulating brain functions. Molecular protein structural elements of rat sarcoma (RAS) and RAS homolog protein enriched in brain (RHEB) GTPases involved in this switch are discussed including their subcellular membrane localization for triggering specific signaling pathways resulting in regulation of synaptic connectivity, axonal growth, differentiation, migration, cytoskeletal dynamics, neural protection, and apoptosis. A beneficial role of neuronal H-RAS activity is suggested from cellular and animal models of neurodegenerative diseases. Recent experiments on optogenetic regulation offer insights into the spatiotemporal aspects controlling RAS/mitogen activated protein kinase (MAPK) or phosphoinositide-3 kinase (PI3K) pathways. As optogenetic manipulation of cellular signaling in deep brain regions critically requires penetration of light through large distances of absorbing tissue, we discuss magnetic guidance of re-growing axons as a complementary approach. In Parkinson’s disease, dopaminergic neuronal cell bodies degenerate in the substantia nigra. Current human trials of stem cell-derived dopaminergic neurons must take into account the inability of neuronal axons navigating over a large distance from the grafted site into striatal target regions. Grafting dopaminergic precursor neurons directly into the degenerating substantia nigra is discussed as a novel concept aiming to guide axonal growth by activating GTPase signaling through protein-functionalized intracellular magnetic nanoparticles responding to external magnets.
Author: | Hendrik SchönebornORCiDGND, Fabian RaudzusORCiDGND, Mathieu CoppeyGND, Sebastian NeumannORCiDGND, Rolf HeumannORCiDGND |
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URN: | urn:nbn:de:hbz:294-64551 |
DOI: | https://doi.org/10.3390/ijms19124052 |
Parent Title (English): | International journal of molecular sciences |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2019/05/22 |
Date of first Publication: | 2018/12/14 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds; RAS GTPase Magneto Protein Therapy; Parkinson’s disease; RHEB GTPase; axonal guidance; brain regeneration; magnetogenetics; nanoparticle; optogenetics; survival |
Volume: | 19 |
Issue: | 12 |
First Page: | 4052-1 |
Last Page: | 4052-37 |
Note: | International journal of molecular sciences, Bd. 19, Artikelnummer 4052 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Lehrstuhl Biochemie II, Arbeitsgruppe Molekulare Neurobiochemie |
Dewey Decimal Classification: | Naturwissenschaften und Mathematik / Chemie, Kristallographie, Mineralogie |
open_access (DINI-Set): | open_access |
faculties: | Fakultät für Chemie und Biochemie |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |