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PLoS One ; 16(10): e0258289, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34634077

RESUMO

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.


Assuntos
Fator Neurotrófico Derivado de Linhagem de Célula Glial/farmacologia , Neurônios/fisiologia , Proteínas Recombinantes/farmacologia , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Modelos Animais de Doenças , Escherichia coli , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Fator Neurotrófico Derivado de Linhagem de Célula Glial/uso terapêutico , Células HEK293 , Humanos , Camundongos Endogâmicos C57BL , Crescimento Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Células PC12 , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Ratos , Proteínas Recombinantes/uso terapêutico , Tirosina 3-Mono-Oxigenase/metabolismo
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