Neurotropic factors (NTFs) comprise an important group of secreted proteins regulating the life cycle of neurons during development. NTFs prevent apoptosis and control the number of neurons innervating a target tissue. NTFs also regulate migration, differentiation and maturation of postmitotic neuronal precursors and promote the regeneration of neurons after injury.

Cerebral dopamine neurotrophic factor (CDNF) is a member of a sub-family of NTF proteins. The premature form of the protein consists of 187 amino acids while the mature form contains 161 residues. CDNF has a saposin-like N-terminal domain and an unstructured carboxy C-terminal domain with an intradomain cysteine bridge in a CXXC motif. Notably, saposin-like proteins interact with lipids, suggesting that CDNF’s N-terminal may also interact with lipids. The saposin-like domain of CDNF crystalizes as a dimer at pH 4.6. It is presumed that CDNF functions upon synthesis and secretion since it does not contain prosequences for enzymatic activation.

When CDNF is injected into the striatum of rats after the injection of 6-OHDA (6-OHDA leads to protracted retrograde degeneration of the nigrostriatal pathway) it significantly reduces amphetamine-induced rotational behavior and protects tyrosine hydroxylase (TH) positive dopaminergic cell bodies in the SN and TH-positive fibers in the striatum. In addition, CDNF had showed neurorestorative effects in the same animal model.

Currently it is still unknown if CDNF also affects other types of neurons in the CNS or whether it has any effect on the PNS. It is also not clear to which target molecule CDNF binds and what signaling pathways it activates. CDNF might serve as a therapeutic agent for neurodegenerative diseases¹.