Neuroinductive properties of mGDNF depend on the producer, E. Coli or human cells

The glial cell line-derived neurotrophic factor (GDNF) is involved in the survival of dopaminergic neurons. Besides, GDNF can also induce axonal growth and creation of new functional synapses. GDNF potential is promising for translation to treat diseases associated with neuronal death: neurodegenera...

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Veröffentlicht in:PloS one 2021-10, Vol.16 (10), p.e0258289
Hauptverfasser: Shamadykova, Dzhirgala V, Panteleev, Dmitry Y, Kust, Nadezhda N, Savchenko, Ekaterina A, Rybalkina, Ekaterina Y, Revishchin, Alexander V, Pavlova, Galina V
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container_title PloS one
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creator Shamadykova, Dzhirgala V
Panteleev, Dmitry Y
Kust, Nadezhda N
Savchenko, Ekaterina A
Rybalkina, Ekaterina Y
Revishchin, Alexander V
Pavlova, Galina V
description The glial cell line-derived neurotrophic factor (GDNF) is involved in the survival of dopaminergic neurons. Besides, GDNF can also induce axonal growth and creation of new functional synapses. GDNF potential is promising for translation to treat diseases associated with neuronal death: neurodegenerative disorders, ischemic stroke, and cerebral or spinal cord damages. Unproductive clinical trials of GDNF for Parkinson's disease treatment have induced to study this failure. A reason could be due to irrelevant producer cells that cannot perform the required post-translational modifications. The biological activity of recombinant mGDNF produced by E. coli have been compared with mGDNF produced by human cells HEK293. mGDNF variants were tested with PC12 cells, rat embryonic spinal ganglion cells, and SH-SY5Y human neuroblastoma cells in vitro as well as with a mouse model of the Parkinson's disease in vivo. Both in vitro and in vivo the best neuro-inductive ability belongs to mGDNF produced by HEK293 cells. Keywords: GDNF, neural differentiation, bacterial and mammalian expression systems, cell cultures, model of Parkinson's disease.
doi_str_mv 10.1371/journal.pone.0258289
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Coli or human cells</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-10-11</date><risdate>2021</risdate><volume>16</volume><issue>10</issue><spage>e0258289</spage><pages>e0258289-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The glial cell line-derived neurotrophic factor (GDNF) is involved in the survival of dopaminergic neurons. Besides, GDNF can also induce axonal growth and creation of new functional synapses. GDNF potential is promising for translation to treat diseases associated with neuronal death: neurodegenerative disorders, ischemic stroke, and cerebral or spinal cord damages. Unproductive clinical trials of GDNF for Parkinson's disease treatment have induced to study this failure. A reason could be due to irrelevant producer cells that cannot perform the required post-translational modifications. The biological activity of recombinant mGDNF produced by E. coli have been compared with mGDNF produced by human cells HEK293. mGDNF variants were tested with PC12 cells, rat embryonic spinal ganglion cells, and SH-SY5Y human neuroblastoma cells in vitro as well as with a mouse model of the Parkinson's disease in vivo. Both in vitro and in vivo the best neuro-inductive ability belongs to mGDNF produced by HEK293 cells. Keywords: GDNF, neural differentiation, bacterial and mammalian expression systems, cell cultures, model of Parkinson's disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>34634077</pmid><doi>10.1371/journal.pone.0258289</doi><tpages>e0258289</tpages><orcidid>https://orcid.org/0000-0003-3665-667X</orcidid><oa>free_for_read</oa></addata></record>
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subjects 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Atomic properties
Biological activity
Biology and Life Sciences
Cell differentiation
Cell survival
Clinical trials
Diagnosis
Disease Models, Animal
Dopamine receptors
Dorsal root ganglia
E coli
Engineering and Technology
Escherichia coli
Experiments
Ganglia, Spinal - drug effects
Ganglia, Spinal - metabolism
Ganglion cells
Glial cell line-derived neurotrophic factor
Glial Cell Line-Derived Neurotrophic Factor - pharmacology
Glial Cell Line-Derived Neurotrophic Factor - therapeutic use
Health aspects
HEK293 Cells
Humans
Ischemia
Medical research
Medical treatment
Medicine and Health Sciences
Mice
Mice, Inbred C57BL
Movement disorders
Nervous system diseases
Neuroblastoma
Neuroblastoma cells
Neuroblasts
Neurodegenerative diseases
Neuronal Outgrowth - drug effects
Neuronal-glial interactions
Neurons - drug effects
Neurons - physiology
Neurophysiology
Neuroprotective Agents - pharmacology
Neuroprotective Agents - therapeutic use
Parkinson Disease - drug therapy
Parkinson Disease - pathology
Parkinson's disease
PC12 Cells
Pheochromocytoma cells
Post-translation
Producer cells
Proteins
Rats
Recombinant Proteins - pharmacology
Recombinant Proteins - therapeutic use
Research and Analysis Methods
Spinal cord
Spinal ganglia
Synapses
Tyrosine 3-Monooxygenase - metabolism
title Neuroinductive properties of mGDNF depend on the producer, E. Coli or human cells
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