Neurotrophins

GDNF is a disulfide-linked, homodimeric neurotrophic factor structurally related to Artemin, Neurturin and Persephin.  These proteins belong to the cysteine-knot superfamily of growth factors that assume stable dimeric protein structures.  GDNF signals through a multicomponent receptor system, composed of a RET and one of the four GFRα (α1-α4) receptors.  GDNF specifically promotes dopamine uptake and survival, and morphological differentiation of midbrain neurons.  Using a Parkinson’s disease mouse model, GDNF has been shown to improve conditions such as bradykinesia, rigidity, and postural instability.  The functional human GDNF ligand is a disulfide-linked homodimer consisting of two 15 kDa polypeptide chains called monomers.  Each monomer contains seven conserved cysteine residues, including Cys-101, which is used for inter-chain disulfide bridging, and others that are involved in the intramolecular ring formation known as the cysteine-knot configuration. The calculated molecular weight of Recombinant Human GDNF is 30.4 kDa.