However, these mice neither displayed increased food intake nor had reduced hypothalamic expression of the proprotein convertase 1 gene PCSK1 or its upstream regulator NHLH2, which have recently been suggested to be key mediators of PWS pathogenesis.
While these compelling results support a critical role for PC1 deficiency in PWS, more work needs to be done to fully understand how and to what extent loss of this prohormone processing enzyme underlies disease manifestations in PWS patients.
Here, we found that protein and transcript levels of nescient helix loop helix 2 (NHLH2) and the prohormone convertase PC1 (encoded by PCSK1) were reduced in PWS patient induced pluripotent stem cell-derived (iPSC-derived) neurons.