Perspectives of RAS and RHEB GTPase signaling pathways in regenerating brain neurons
| Autor: | Hendrik, Schöneborn, Fabian, Raudzus, Mathieu, Coppey, Sebastian, Neumann, Rolf, Heumann |
|---|---|
| Přispěvatelé: | Ruhr-Universität Bochum [Bochum], Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Neurogenesis
Parkinson's disease brain regeneration RHEB GTPase Review survival lcsh:Chemistry Cell Movement Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology optogenetics lcsh:QH301-705.5 magnetogenetics axonal guidance nanoparticle Brain Cell Differentiation RAS GTPase Magneto Protein Therapy lcsh:Biology (General) lcsh:QD1-999 nervous system ddc:540 ras Proteins Parkinson’s disease Ras Homolog Enriched in Brain Protein Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences International Journal of Molecular Sciences, MDPI, 2018, 19 (12), pp.4052. ⟨10.3390/ijms19124052⟩ International Journal of Molecular Sciences, Vol 19, Iss 12, p 4052 (2018) |
| ISSN: | 1661-6596 1422-0067 |
| DOI: | 10.3390/ijms19124052⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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