About CDNF:
CDNF, also known as Cerebral dopamine neurotrophic factor belongs to the CDNF/mesencephalic astrocyte-derived neurotrophic MANF family for neurotrophic factors. These are responsible for demonstrating neurotrophic activities in dopaminergic neurons.
CDNF Mechanism
Studies have been completed to explore the mechanism of neuroprotection through CDNF. Research suggests that focal cerebral ischemia is a vivo ER stress model and as such will reduce the accumulation of proteins within the ER. Investigating the CDNF expression in the cerebral cortex, research has shown that an increased level of CDNF positive cells was apparent in the peri-infarct tissue. This was after 2 hours of ischemia as well as 24 hours of reperfusion.
Research also has been conducted to explore the subpopulation of CDNF positive cells. This highlights that certain CDNF positive cells were typically colocalized and formed with NeuN-positive cells.
Researchers have suggested that exploring the mechanisms of the effects of CDNF on a stroke may potentially lead to an increase in therapeutic possibilities for patients.
CDNF Interaction
CDNF protein does seem to interact and act differently in the human brain compared to similar neurotrophic factors. It may be able to protect and repair dopamine neurons and has been explored through clinical trials. GDNF acts through a typical neurotrophic mechanism and has a similar profile. It is, therefore, useful to explore whether CDNF could interact in a similar form.
Studies have explored the impact of CDNF treatment on conditions such as Parkinson’s disease through interactions with drugs. Treatment for Parkinson’s is largely focused on reducing motor symptoms. Through Parkinson’s there is dopamine neuron damage, reducing the impact and the effect of drugs like levodopa. It has been suggested that CDNF treatment could reduce neuron damage and improve functioning, increasing levodopa treatment.
It is hoped that CDNF is more effective than GDNF at providing support for patients suffering from Parkinson's and the impact of these conditions. It is believed this could be the case due to acting with a different mechanism and thus providing an altered interaction.
CDNF Function
Research has shown that CDNF has various functions including the ability to reduce infarct volume, lower the level of apoptotic cells and increase motor function. These studies have been explored used rats as subjects. Furthermore, CDNF is also able to increase the cell viability of astrocytes and neurons that are treated by OGD. This does suggest that CDNF could be relevant for treating ischemic injury in patients.
Furthermore, the expression profile of CDNG in the primary neurons that have been treated with ER stress-inducing agents as well as in ischemic brain suggests that a protective mechanism of CDNF could be apparent through ER stress.
CDNF Structure
CDNF has a structure which includes two domains. These are a presumed unstructured C-terminal domain. It has an intradomain cysteine bridge that exists in a CRAC motif. There is also a saposin similar N-terminal domain. At the very edge of the C-terminus, it has a lysine-threonine-glutamic acid-leucine. This does have a similar structure to the classic ER retention signal. Overall, this suggests that CNF could have crucial functions in the endoplasmic reticulum.