Treating Parkinson's the CDNF Way

Science's STKE  10 Jul 2007:
Vol. 2007, Issue 394, pp. tw245
DOI: 10.1126/stke.3942007tw245

Lindholm et al. report the cloning, molecular characterization, and tissue expression of a member of a new family of neurotrophins. Through sequence analysis, they identified a gene similar to that encoding mesencephalic-astrocyte-derived neurotrophic factor (MANF, also known as ARMET) and named the new protein conserved dopamine neurotrophic factor (CDNF, which in genomic databases was called ARMETL1 for ARMET-like 1). CDNF was secreted when heterologously expressed in human cultured cell lines or the insect cell line Sf9. Electrospray ionization-mass spectrometry analysis of the secreted protein indicated that the protein formed four disulfide bridges with the eight conserved cysteines. Transcript analysis in mice revealed that CDNF was expressed in several tissues during embryogenesis and postnatally. In the brain, in situ protein analysis showed that the protein was present in the somas of neurons. Although MANF was previously reported to promote survival of dopaminergic neurons in vitro, Lindholm et al. show that in a rat model of Parkinson's disease, injection of CDNF before or after exposure to the neurotoxin prevented or ameliorated symptoms and reduced the loss of dopaminergic neurons in the substantia nigra.

P. Lindholm, M. H. Voutilainen, J. Laurén, J. Peränen, V.-M. Leppänen, J.-O. Andressoo, M. Lindahl, S. Janhunen, N. Kalkkinen, T. Timmusk, R. K. Tuominen, M. Saarma, Novel neurotrophic factor CDNF protects and rescues midbrain dopamine neurons in vivo. Nature 448, 73-77 (2007). [PubMed]