A novel mTOR activating protein protects dopamine neurons against oxidative stress by repressing autophagy related cell death.

Our previous microarray analysis identified a neuroprotective protein Oxi-alpha, that was down-regulated during oxidative stress (OS)-induced cell death in dopamine neurons [Neurochem. Res. (2004) vol.

The dopamine D2 receptor regulates the development of dopaminergic neurons via extracellular signal-regulated kinase and Nurr1 activation.

Because the dopaminergic pathways in the midbrain have been closely associated with serious neuropsychiatric disorders, the elucidation of the mechanisms underlying dopaminergic neuronal development should provide some important clues for related disorders. In mice lacking the dopamine D2 receptor (D2R-/-), stereological cell counting analysis showed that the number of mesencephalic tyrosine hydroxylase (TH) cells was significantly low during ontogeny, compared with that observed in wild-type (WT) mice, thereby indicating an alteration in dopaminergic neuronal development in the absence of D2R. The results of immunohistochemical and reverse transcription-PCR analyses revealed that the expression of Nurr1, an orphan nuclear receptor, as well as Ptx3 expression, was selectively reduced in D2R-/- mice during the embryonic stage.