Neurotrophins are synthesized as precursors called pro-neurotrophins and then mature neurotrophins are formed proteolytically from them. Recent findings revealed that pro- and mature neurotrophins elicit opposite functional effects on cell survival, highlighting the importance of this processing step. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) belong to the neurotrophin family and are mutually homologous, but BDNF is less efficiently processed. In order to find the reason for this, we examined some possibilities by using PC12 cells, and found that the pro-region, especially the last half of it, affected very much the processing efficiency of these neurotrophins. (c) 2007 Elsevier Inc. All rights reserved.