Proteolytic cleavage of proBDNF to mBDNF in neuropsychiatric and neurodegenerative diseases

•mBDNF/proBDNF plays a key role in neuropsychiatric and degenerative diseases.•ProBDNF is proteolytically cleaved into mBDNF by several proteases.•These proteases could be new targets in neuropsychiatric and degenerative diseases. Brain-derived neurotrophic factor (BDNF) is involved in pathophysiological mechanisms in neuropsychiatric diseases, including depression, anxiety, and schizophrenia (SZ), as well as neurodegenerative diseases like Parkinson’s disease (PD) and Alzheimer’s disease (AD). An imbalance or insufficient pro-brain-derived neurotrophic factor (proBDNF) transformation into mature BDNF (mBDNF) is potentially critical to the disease pathogenesis by impairing neuronal plasticity as suggested by results from many studies. Thus, promoting proBDNF transformation into mBDNF is therefore hypothesized as beneficial for the treatment of neuropsychiatric and neurodegenerative diseases. ProBDNF is proteolytically cleaved into the mBDNF by intracellular furin/proprotein convertases and extracellular proteases (plasmin/matrix metallopeptidases). This article reviews the mechanisms of the conversion of proBDNF to mBDNF and the research status of intracellular/extracellular proteolytic proteases for neuropsychiatric and neurodegenerative disorders.