Induction of neural differentiation by the transcription factor neuroD2.

Pro-neural basic helix loop helix (bHLH) transcription factors are involved in many aspects of normal neuronal development, and over-expression of genes for several of these factors has been shown to induce aspects of neuronal differentiation in cell lines and stem cells. Here we show that over-expression of NeuroD2 (ND2), Neurogenin1 and 2 leads to morphological differentiation of N18-RE-105 neuroblastoma cells and increased expression of synaptic proteins. Particularly ND2 induced neurite formation and increases in the expression of synaptic proteins such as synaptotagmin, that is not expressed normally in this cell type, as well as the redistribution of another synaptic protein, SNAP25, to a cell membrane location.

Induction of tyrosine hydroxylase expression by the transcription factor Pitx3.

Transcription factors are fate determining regulatory factors in dopaminergic neuronal development and differentiation. Among them, Nurr1 is the most extensively studied, but the importance of Pitx3 has recently been appreciated. Over-expression of both factors has been utilized to enhance the dopaminergic differentiation of stem cells for transplantation into models of Parkinson's disease.

An in vitro model of inflammatory neurodegeneration and its neuroprotection.

Inflammation has been implicated in a variety of acute and chronic neurodegenerative diseases in which the inflammatory processes are considered not only to result from neurodegenerative effects, but also to contribute to these effects. To investigate the primary effect of inflammation on neuronal survival, a co-culture system of neuronal cells (differentiated SH SY5Y human neuroblastoma cells or primary cortical/striatal neurons) and monocytic cells (THP-1) in direct cell-cell contact was set up. After 5 days, THP-1 activation by lipopolysaccharide and phorbol 12-myristate 13-acetate resulted in a significant increase of neuronal cell death compared to co-culture without activation.