The nerve growth factor NGF belongs to the neurotrophin protein family and promotes growth, maintenance and differentiation of neuronal cells. NGF is synthesized as a pro-protein (ProNGF) and secreted upon tissue specific processing to mature NGF. In contrast to NGF, which is known with cell proliferative function ProNGF acts probably as pro-apoptotic molecule. Neither the structure of the pro-peptide nor the type of interaction between pro-peptide and the mature domain is unknown for NGF and all neurotrophins. It could be demonstrated, that the presents of the pro-peptide has no influence to the very slow unfolding of the NGF domain. Thereby, the slow unfolding of NGF, which was described as an unthreading of the cystine knot (loop-threading hypothesis), could be explained by a loss of the residue structure, which is located near the cystine knot. The characterisation of the isolated pro-peptide and the NGF-coupled pro-peptide showed that only the NGF-coupled pro-peptide contains stabilising tertiary contacts. Two folding intermediates could be identified and characterised during the folding and unfolding of NGF-coupled pro-peptide. Furthermore, a region inside the pro-peptide and an amino acid residue inside the mature part could be identified, which are involved in the pro-peptide NGF interaction. Thereby, this amino acid residue inside the NGF is also a part of the receptor association of NGF to TrkA and p75, which explains the observed lower binding affinity of ProNGF to those receptors.