Neurotrophins

CDNF is localized mainly in the cavity of the endoplasmic reticulum (ER) and does not have receptors on the cell membrane . Its primary function is to regulate ER stress, and it can also suppress inflammation and apoptosis . CDNF is expressed in various tissues, including the brain, where it plays a crucial role in the maturation and maintenance of neurotransmitter systems . It is also involved in regulating neuroplasticity and non-motor behavior .

The primary biological function of CDNF is to protect and restore dopamine neurons, particularly in the context of neurodegenerative diseases like Parkinson’s disease . CDNF functions both as an extracellular trophic factor and as an intracellular ER luminal protein that protects neurons and other cell types against ER stress . It also plays a role in suppressing neuroinflammation and apoptosis .

CDNF interacts with other molecules and cells through various mechanisms. It forms a complex with the regulatory, nucleotide-binding domain of GRP78, the master regulator of the unfolded protein response (UPR) pathway . This interaction helps CDNF regulate ER stress-induced UPR signaling and promote protein homeostasis in the ER . CDNF can function both extracellularly and intracellularly, providing neuroprotective effects through these interactions .

The expression and activity of CDNF are regulated through various mechanisms. CDNF is secreted by the cell and binds to receptors on the plasma membrane, triggering downstream signaling pathways such as the extracellular signal-regulated kinase pathway (Ras/ERK) or the phosphatidylinositol 3-kinase pathway (PI3K/Akt) . These signaling cascades mediate synapse formation, survival, differentiation, and neuronal maturation . Additionally, CDNF can regulate ER stress-induced UPR signaling and promote protein homeostasis in the ER .

CDNF has significant potential in biomedical research, particularly in the context of neurodegenerative diseases like Parkinson’s disease . It has demonstrated protective and restorative properties in various models of neuropathology associated with ER stress . CDNF is also being explored as a therapeutic strategy for other neurodegenerative protein-misfolding diseases . Its ability to regulate ER stress and suppress inflammation and apoptosis makes it a promising candidate for future therapies .

Throughout the life cycle, CDNF plays a crucial role in regulating neurogenesis and the maturation of neurotransmitter systems . It is involved in shaping the neurotransmitter circuit structure, seizure susceptibility, and complex behaviors . CDNF’s protective and restorative properties make it essential for maintaining neuronal health from development to aging and disease .