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

Dzhirgala V Shamadykova; Dmitry Y Panteleev; Nadezhda N Kust; Ekaterina A Savchenko; Ekaterina Y Rybalkina; Alexander V Revishchin; Galina V Pavlova

doi:10.1371/journal.pone.0258289

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

PLoS One. 2021 Oct 11;16(10):e0258289. doi: 10.1371/journal.pone.0258289. eCollection 2021.

Authors

Dzhirgala V Shamadykova^{1

2}, Dmitry Y Panteleev¹, Nadezhda N Kust², Ekaterina A Savchenko³, Ekaterina Y Rybalkina⁴, Alexander V Revishchin¹, Galina V Pavlova^{1

3

5}

Affiliations

¹ Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia.
² Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
³ Burdenko Neurosurgical Institute, Moscow, Russia.
⁴ Blokhin Russian Cancer Research Center, Moscow, Russia.
⁵ Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Moscow, Russia.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Disease Models, Animal
Escherichia coli
Ganglia, Spinal / drug effects
Ganglia, Spinal / metabolism
Glial Cell Line-Derived Neurotrophic Factor / pharmacology*
Glial Cell Line-Derived Neurotrophic Factor / therapeutic use
HEK293 Cells
Humans
Mice
Mice, Inbred C57BL
Neuronal Outgrowth / drug effects
Neurons / drug effects
Neurons / physiology*
Neuroprotective Agents / pharmacology
Neuroprotective Agents / therapeutic use
PC12 Cells
Parkinson Disease / drug therapy
Parkinson Disease / pathology
Rats
Recombinant Proteins / pharmacology*
Recombinant Proteins / therapeutic use
Tyrosine 3-Monooxygenase / metabolism

Substances

Glial Cell Line-Derived Neurotrophic Factor
Neuroprotective Agents
Recombinant Proteins
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Tyrosine 3-Monooxygenase

Grants and funding

G.P. received grant funding. This research was funded by the Ministry of Science and Higher Education of the Russian Federation (grant number 075-15-2020-809 (13.1902.21.0030) and RFBR (grant number 18-29-01-012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.