Cathepsin D deficiency delays central nervous system myelination by inhibiting proteolipid protein trafficking from late endosome/lysosome to plasma membrane

Cathepsin D regulates the transport of the major component of myelin, proteolipid protein (PLP), to the cell membrane. The enzyme cathepsin D is involved in the breakdown of proteins but little is known about how mutations in cathepsin D are associated with fatal neurological diseases. A team of Chinese researchers led by Shu-Yi Pan at the Navy General Hospital of PLA in Beijing examined the effects of cathepsin D deficiency on the formation of a protective sheath around nerves, a process known as myelination, in mice. They found a marked decrease in the number of mature myelin-producing cells in the brains of mice lacking cathepsin D. Furthermore, in these cells PLP-containing vesicles were transported more slowly towards the plasma membrane than in the controls, highlighting a potential mechanism through which cathepsin D regulates myelination.