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

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

doi:10.1371/journal.pone.0258289

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.

Highlights

To date, neurotrophic factors are the most potent mediators of neuronal survival and inducers of their differentiation
The goal of this study was to evaluate the functional significance of mature GDNF (mGDNF) as a neuronal inducer as well as its dependence on the producer, E. coli and mammalian (HEK293) cells
It should be noted that, apart from the identification of glial cell-derived neurotrophic factor (GDNF) isoforms optimal for neuronal regeneration, it is critical to compare the function of GDNF synthesized in E. coli and mammalian cells

Summary

Introduction

Neurotrophic factors are the most potent mediators of neuronal survival and inducers of their differentiation. The glial cell-derived neurotrophic factor (GDNF) is given particular attention among neurotrophic factors. GDNF was identified in the medium conditioned by a glial cell line based on the capacity to promote neuronal survival as well as cell enlargement and neurite elongation in mesencephalic dopaminergic neurons in vitro [1]. GDNF was initially considered as a selective survival factor of nigrostriatal dopaminergic neurons [2].

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