Glial cell line-derived neurotrophic factor (GDNF) (GDNF)

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor essential for the survival and maintenance of various neuronal populations, most notably the midbrain dopaminergic neurons [1]. It belongs to the GDNF family of ligands (GFLs), which are distant members of the transforming growth factor-beta (TGF-β) superfamily [2]. GDNF signals through a multicomponent receptor complex consisting of the GDNF family receptor alpha-1 (GFRα1) coreceptor and the RET receptor tyrosine kinase, activating downstream pathways such as PI3K/Akt and MAPK/ERK that promote cell survival and differentiation [3]. In neurodegenerative conditions like Parkinson's disease, GDNF levels or signaling are often compromised, making it a primary target for neuroprotective and regenerative therapies [4]. "Plasmid GDNF DNA" refers to a non-viral gene therapy modality where a plasmid encoding the GDNF gene is delivered to target tissues, such as the putamen, to induce local production of the protein [5]. While clinical trials using various delivery methods (including viral vectors and direct protein infusion) have shown mixed results regarding efficacy, GDNF remains a high-priority target for halting disease progression in Parkinson's and other neurodegenerative disorders [6].

Other names

ATF1ATF2HFB1-GDNFHSCR3Astrocyte-derived trophic factorGlial cell line-derived neurotrophic factor precursor

The therapeutic approach involves the delivery of a DNA plasmid encoding the GDNF gene, which is then expressed by host cells to produce functional GDNF protein. This protein acts as an agonist for the GFRα1/RET receptor complex, promoting the survival, repair, and functional restoration of dopaminergic neurons.