Unique neuronal functions of cathepsin L and cathepsin B in secretory vesicles: biosynthesis of peptides in neurotransmission and neurodegenerative disease.

Proteases are required for the production of peptide neurotransmitters and toxic peptides in neurodegenerative diseases. Unique roles of the cysteine proteases cathepsin L and cathepsin B in secretory vesicles for the production of biologically active peptides have been demonstrated in recent studies. Secretory vesicle cathepsin L participates in the proteolytic conversion of proenkephalin into the active enkephalin, an opioid peptide neurotransmitter that mediates pain relief. Moreover, recent findings provide evidence that cathepsin B in regulated secretory vesicles participates in the production of toxic beta-amyloid peptides that are known to accumulate extracellularly in Alzheimer's disease brains. The neurobiological functions of cathepsins L and B demonstrate that these secretory vesicle cysteine proteases produce biologically active peptides. These results demonstrate newly identified roles for cathepsins L and B in neurosecretory vesicles in the production of biologically active peptides.