FIGURE 2.
Schematic presentation of BDNF synthesis from translation, intracellular processing through to its secretion. BDNF is synthesized from the BDNF gene in a multi-step process. Intracellularly, the pre-pro BDNF is produced in the endoplasmic reticulum which is then translocated toward the Golgi apparatus, where the pre-sequence is cleaved off to form pro- BDNF. The pro-BDNF is further processed, via the Golgi apparatus, into the trans-Golgi network (TGN) where the pro domain is cleaved off by proteases to form mature BDNF (BDNF). The pro-BDNF is proteolytically cleaved by furin or convertase and is intracellularly secreted as BDNF. Both pro-BDNF and BDNF are preferentially grouped and packaged into secretory dense core-vesicles and secreted extracellularly via exocytosis. The extracellularly secreted pro-BDNF is then processed and catalyzed by proteases such as plasmin and metalloproteinases (MMP2 and MMP9) to form BDNF. As a result, three functionally active isoforms, namely pro-domain, pro-BDNF and BDNF are secreted extracellularly. Adapted from Kowianski et al. (2018).