title: The Transcription Factor NURR1 Exerts Concentration-Dependent Effects on Target Genes Mediating Distinct Biological Processes.
abstract: The transcription factor NURR1 plays a pivotal role in the development and maintenance of neurotransmitter phenotype 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.
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine Detroit, MI, USA.
authors.forename: Magen M
authors.initials: MM
authors.lastname: Johnson
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Michelhaugh
authors.forename: Mohamad
authors.initials: M
authors.lastname: Bouhamdan
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Schmidt
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bannon