Finally, the protein precursor undergoes proteolysis due to a proteolytic consensus sequence in its C-terminus end and is cleaved to 134 amino acids.

Because multiple proteases can cleave the protein precursor, four different mature forms of GDNF can be produced.

GDNF also regulates kidney development and spermatogenesis, and has a powerful and rapid negative (ameliorating) effect on alcohol consumption.

[9] Glial cell line-derived neurotrophic factor has been shown to interact with GFRA1[9][17] and GDNF family receptor alpha 1.

[11] The intensity and duration of RET signaling can likewise be monitored by the GPI-anchor of GFRα1 by interacting with compartments of the cell membrane, such as lipid rafts or cleavage by phospholipases.

The association between GDNF and NCAM results in the activation of cytoplasmic protein tyrosine kinases Fyn and FAK.

[20] In 2012, the University of Bristol began a five-year clinical trial on Parkinson's sufferers, in which surgeons introduced a port into the skull of each of the 41 participants through which the drug could be delivered, in order to enable it to reach the damaged cells directly.

[21] The results of the double-blind trial, where half the participants were randomly assigned to receive regular infusions of GDNF and the other half placebo infusions, did not show a statistically significant difference between the active treatment group and those who received placebo, but did confirm the effects on damaged brain cells.

Renishaw plc manufactured the CED device on behalf of North Bristol NHS Trust and provided additional technical and analytical support.

[24] Administration of the African hallucinogen ibogaine potently increases GDNF expression in the ventral tegmental area, which is the mechanism behind the alkaloid's anti-addictive effect.

[25] Rodent models for a non-psychedelic analogue of this compound show promise in promoting GDNF expression without the hallucinogenic or cardiotoxic effects well documented for ibogaine.