METHOD FOR INDUCING IMPROVED DOPAMINERGIC NEURONS BY MUTANT NURR1 GENE EXPRESSION

摘要

The present invention provides a method for inducing dopaminergic neurons. The method comprises in vitro gene transfection to enable expression of a mutant Nurr1 gene in neural precursor cells, in which Akt-phosphorylation is significantly reduced by mutation of the conserved Akt-phosphorylation site of a Nurr1 protein. Further, the present invention provides transfected neural precursor cells enabling expression of the mutant Nurr1 gene in which Akt-phosphorylation is significantly reduced by mutation of the conserved Akt-phosphorylation site of the Nurr1 protein. In addition, the present invention provides a dopaminergic neural cell population induced from the neural precursor cells by expressing the mutant Nurr1 gene in the neural precursor cells. According to the present invention, the induction of the mutant protein expression in the neural precursor cells can generate dopaminergic neurons which are able to maintain Nurr1 protein concentration stably and natural Nurr1 function. The dopaminergic neurons produced by the mutant Nurr1 gene are resistant to toxic stimulation and ensure improved in vitro and in vivo viability after transplanting into a rat brain.