Conserved dopamine neurotrophic factor (CDNF)

Conserved dopamine neurotrophic factor (CDNF), also frequently referred to as cerebral dopamine neurotrophic factor, is an evolutionarily conserved protein that functions as a potent neuroprotective and neurorestorative agent (Lindholm et al., 2007). Unlike traditional neurotrophic factors like BDNF that signal through cell-surface tyrosine kinase receptors, CDNF is primarily an endoplasmic reticulum (ER)-resident protein that is secreted in response to cellular stress (Huttunen et al., 2016). Its primary mechanism of action involves the regulation of the unfolded protein response (UPR) and the mitigation of ER stress-induced apoptosis, which are central to the pathogenesis of several neurodegenerative disorders (Voutilainen et al., 2015). In animal models of Parkinson's disease, CDNF has demonstrated the ability to protect dopaminergic neurons from toxin-induced death and even restore function in already damaged neurons by improving proteostasis. Clinical development, led by companies like Herantis Pharma, has focused on recombinant human CDNF delivered via intracranial infusion to slow disease progression in Parkinson's patients (NCT03295786). Beyond Parkinson's, CDNF is being explored for its therapeutic potential in amyotrophic lateral sclerosis (ALS) and other protein-misfolding diseases due to its unique ability to support cell survival under chronic stress.

Other names

Cerebral dopamine neurotrophic factorARMET-like protein 1ARMETL1

CDNF acts by modulating the unfolded protein response (UPR) and reducing endoplasmic reticulum (ER) stress, thereby preventing apoptosis and promoting the survival and functional recovery of stressed neurons (Huttunen et al., 2016; Voutilainen et al., 2015).