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Quantification of Hypopigmentation Activity In Vitro
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Pharmacological BACE1 and BACE2 inhibition induces hair depigmentation by inhibiting PMEL17 processing in mice

Derya R Shimshek1, Laura H Jacobson1, Carine Kolly2

  • 1Neuroscience, Novartis Institutes for BioMedical Research, 4002 Basel, Switzerland.

Scientific Reports
|February 26, 2016
PubMed

Insights

Inhibition of Beta Site APP Cleaving Enzyme-2 (BACE2) impairs hair pigment production. Dual BACE1/BACE2 inhibition causes irreversible hair depigmentation in mice, impacting melanosome maturation.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Dermatology

Background:

  • Melanocytes produce melanin for hair color.
  • Pigment cell-specific MELANOCYTE PROTEIN (PMEL17) is crucial for melanogenesis.
  • Beta Site APP Cleaving Enzyme-2 (BACE2) processes PMEL17.

Purpose of the Study:

  • To investigate BACE2's role in PMEL17 processing.
  • To evaluate the effects of BACE1/BACE2 inhibition on hair pigmentation.

Main Methods:

  • In vitro studies using mouse and human melanocytes.
  • In vivo studies using wildtype and BACE2-deficient mice treated with NB-360 inhibitor.
  • Assessment of PMEL17 proteolytic processing and hair depigmentation.

Main Results:

  • BACE2 inhibition impairs PMEL17 processing in melanocytes.
  • Dual BACE1/BACE2 inhibition with NB-360 causes dose-dependent hair depigmentation in mice.
  • No morphological changes observed in retinal pigmented epithelium.

Conclusions:

  • BACE2 is essential for normal PMEL17 processing and hair pigmentation.
  • Combined BACE1 and BACE2 inhibition significantly affects melanosome maturation and induces hair depigmentation.

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