Cerebral dopamine neurotrophic factor (CDNF) (CDNF)

Cerebral dopamine neurotrophic factor (CDNF) is a neuroprotective protein that belongs to a unique family of evolutionarily conserved neurotrophic factors, alongside mesencephalic astrocyte-derived neurotrophic factor (MANF) (Lindholm et al., 2007). Unlike traditional neurotrophins, CDNF is primarily an endoplasmic reticulum (ER)-resident protein that is secreted in response to cellular stress (UniProt, 2024). Its primary biological role involves the regulation of the unfolded protein response (UPR) and the mitigation of ER stress, which are critical pathways in the pathogenesis of various neurodegenerative disorders (Voutilainen et al., 2015). CDNF has demonstrated significant efficacy in preclinical models for protecting and even restoring the function of dopaminergic neurons, leading to its investigation as a disease-modifying therapy for Parkinson's disease (Huttunen and Saarma, 2019). In clinical settings, recombinant CDNF is typically administered via direct intracranial infusion to bypass the blood-brain barrier (Herantis Pharma, 2020). Ongoing research also explores its potential in treating amyotrophic lateral sclerosis (ALS) and other conditions characterized by ER stress-induced neuronal death (Galli et al., 2016).

Other names

ARMETL1Protein ARMET-like 1Conserved dopamine neurotrophic factorCDNF signaling pathway

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 damaged neurons, particularly dopaminergic neurons (Voutilainen et al., 2015; Huttunen and Saarma, 2019).