Pharmacological BACE1 and BACE2 Inhibition Induces Hair Depigmentation by Inhibiting PMEL17 Processing in Mice

February 2016 in “ Scientific reports ”

Derya R. Shimshek, Laura H. Jacobson, Carine Kolly, Nataša Zamurović, Kamal K. Balavenkatraman, Laurent Morawiec, Robert Kreutzer, Juliane Schelle, Mathias Jucker, Barbara Bertschi, Diethilde Theil, Annabelle Heier, Karine Bigot, Karen Beltz, Rainer Machauer, Irena Brzak, Ludovic Perrot, Ulf Neumann

BACE1 BACE2 PMEL17 melanin hair follicle melanocytes BACE2 knockout mice NB-360 hair depigmentation melanosome maturation

TLDR Blocking BACE1 and BACE2 enzymes causes hair color loss in mice.

In the study, researchers investigated the role of Beta Site APP Cleaving Enzyme-1 (BACE1) and BACE2 in hair pigmentation by examining their effect on the processing of PMEL17, a protein crucial for melanin production in hair follicle melanocytes. They found that BACE2 knockout mice exhibited impaired PMEL17 processing, leading to deficient melanin storage and hair depigmentation. The study also showed that treatment with a potent dual BACE1/BACE2 inhibitor, NB-360, caused a dose-dependent depigmentation of hair in wildtype, bace2 +/−, and bace2 −/− mice, which was irreversible. However, there were no morphological changes observed in the retinal pigmented epithelium. These findings suggest that inhibition of BACE2, and to some extent BACE1, can affect melanosome maturation and result in hair depigmentation in mice.