The transcription factor NURR1 plays a pivotal role in the development and maintenance of neurotransmitterphenotype in midbrain dopamine neurons. Conversely, decreased NURR1 expression is associated with a number of dopamine-related CNS disorders, including Parkinson's disease and drug addiction. In order to better understand the nature of NURR1-responsive genes and their potential roles in dopamine neuron differentiation and survival, we used a human neural cellular background (SK-N-AS cells) in which to generate a number of stable clonal lines with graded NURR1 gene expression that approximated that seen in DA cell-rich human substantia nigra. Gene expression profiling data from these NURR1-expressing clonal lines were validated by quantitative RT-PCR and subjected to bioinformatic analyses. The present study identified a large number of NURR1-responsive genes and demonstrated the potential importance of concentration-dependent NURR1 effects in the differential regulation of distinct NURR1 target genes and biological pathways. These data support the promise of NURR1-based CNS therapeutics for the neuroprotection and/or functional restoration of DA neurons. © 2011 Johnson, Michelhaugh, Bouhamdan, Schmidt and Bannon.
CITATION STYLE
Johnson, M. M., Michelhaugh, S. K., Bouhamdan, M., Schmidt, C. J., & Bannon, M. J. (2011). The transcription factor NURR1 exerts concentration-dependent effects on target genes mediating distinct biological processes. Frontiers in Neuroscience, (DEC). https://doi.org/10.3389/fnins.2011.00135
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