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GDNF and the GDNF-family ligands artemin, neurturin and persephin belong to the transforming growth factor-β （TGF-β） superfamily. The TGF-β superfamily represents a collection of multifunctional cytokines, including the neurotrophin family. Although GDNF shows only limited amino-acid sequence homology with the other members of the superfamily, it has significant conformational similarity as they all have the characteristic cysteine knot structural motif with the formation of three disulphide bonds. This family of proteins all function as homodimers and show protective and restorative effects in the developing and adult central nervous system （CNS）. The neurotrophic effects of GDNF appear to be dependent on the presence of TGF-β in both in vivo and in vitro studies.
GDNF was originally isolated from the supernatant of a rat glioma cell-line, and found to have pronounced effects on the survival of midbrain dopaminergic neurons. It has a relatively high specificity for dopaminergic neurons and thus has significant potential for the treatment of PD, which is predominantly characterised by progressive depletion of midbrain dopaminergic cell populations. Subsequently, GDNF has also been found to have trophic and protective effects on noradrenergic neurons in the locus coeruleus, as well as peripheral motor neurons, raising hopes for its therapeutic potential in HD and ALS.