CDNF (conserved dopamine neurotrophic factor), also called Armetl1 (arginine-rich, mutated in early stage tumors-like 1), is a 17‑19 kDa secreted protein that shares 52% amino acid (aa) identity with mouse MANF (mesencephalic-astrocyte-derived neurotrophic factor), also called Armet (1). The Armet designation is not preferred, because the proteins as translated are not actually arginine-rich (1). However, both CDNF and MANF have a high proportion of charged residues, a pattern of eight cysteines shown to form intramoleculular disulfide bonds, and a C-terminal endoplasmic reticulum retention signal (shown to function in MANF) (1‑3). The mouse CDNF cDNA encodes a 187 aa protein with a 24 aa signal sequence and a 163 mature sequence (1). Mature mouse CDNF shares 80%, 87%, 83%, and 82% aa identity with human, rat, equine and bovine CDNF, respectively. Although CDNF mRNA and protein are expressed in pre and postnatal mouse brain, they are mostly abundant in adult heart, skeletal muscle and testis. Transcripts within the postnatal mouse brain are concentrated in the hippocampus, thalamus, corpus callosum and optic nerve (1). Like MANF and GDNF, CDNF promotes survival of dopaminergic neurons in vitro (1, 4). In a rat Parkinson's disease model, CDNF also promotes rescue and restoration of dopaminergic neurons in vivo (1).
