In Parkinson's disease brain dopaminergic neurons degenerate in the midbrain. Neurotrophic factors (NTF) promote the survival, differentiation and maintenance of neurons in developing and adult vertebrate nervous system, and have a great potential for the treatment of neurodegenerative diseases. The most potent NTF for dopaminergic neurons described so far are the glial cell line- derived neurotrophic factor, GDNF and its homolog neurturin¹. We have discovered a novel conserved dopamine neurotrophic factor (CDNF) as a trophic factor for dopaminergic neurons. CDNF and its vertebrate and invertebrate homologs the mesencephalic astrocyte-derived neurotrophic factor (MANF) are secreted proteins with eight conserved cysteine residues defining a novel, evolutionarily conserved NTF family. In vivo, CDNF protected and repaired the nigrostriatal dopaminergic neurons in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson's disease². Our results suggest that CDNF might be beneficial for the treatment of Parkinson's disease. Little is known about the neurotrophic factors in Drosophila. We have described a novel NTF in Drosophila, DmMANF and demonstrated that it is essential for the of maintenance dopaminergic neurites and dopamine levels. The rescue experiments confirm DmMANF as a functional ortholog of the human MANF gene thus opening the window for comparative studies of this novel family of NTF. ¹Bespalov M., Saarma M. (2007) GDNF receptor complex is an emerging drug target. Trends in Pharmacological Sciences 28 (2), 68–74. ²Lindholm, P. et al. and Saarma, M. (2007) Nature, 448, 73–77.