GDNF

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 GFRalpha (alpha1-alpha4) receptors. GDNF specifically promotes dopamine uptake and survival and morphological differentiation of midbrain neurons. Using 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, of two 15 kDa polypeptide chains called monomers. Each monomer contains seven conserved cysteine residues, one of which (Cys 101) is used for inter-chain disulfide bridging and the others are involved in intramolecular ring formation known as the cysteine knot configuration.