ArticleScientific reports2016
Pharmacological BACE1 and BACE2 inhibition induces hair depigmentation by inhibiting PMEL17 processing in mice.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 66 citations in OpenAlex.
- Further analyses of the safety of verubecestat in the phase 3 EPOCH trial of mild-to-moderate Alzheimer's disease.Alzheimer's research & therapy · 2019Trial
- Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of PF-06751979, a Potent and Selective Oral BACE1 Inhibitor: Results from Phase I Studies in Healthy Adults and Healthy Older Subjects.Journal of Alzheimer's disease : JAD · 2019Trial
- The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease.EMBO molecular medicine · 2018Trial
- BACE2 tunes lipid uptake through lipid transporters shedding supporting cancer cell proliferation.Journal of experimental & clinical cancer research : CR · 2026Article
- Elenbecestat and Compound 89 Potently Inhibit BACE1 but Not BACE2 When Subchronically Dosed in Non-Human Primates.Proteomics · 2026Article
- Inhibition of Tyrosinase and Melanogenesis by Carboxylic Acids: Mechanistic Insights and Safety Evaluation.Molecules (Basel, Switzerland) · 2025Article
- The Alzheimer's disease-linked protease BACE2 cleaves VEGFR3 and modulates its signaling.The Journal of clinical investigation · 2024Article
- Review on anti-alzheimer drug development: approaches, challenges and perspectives.RSC advances · 2024Review
- Taking a color photo: A homozygous 25-bp deletion inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Disrupting the Repeat Domain of Premelanosome Protein (PMEL) Produces Dysamyloidosis and Dystrophic Ocular Pigment Reflective of Pigmentary Glaucoma.International journal of molecular sciences · 2023Article
- New Highly Selective BACE1 Inhibitors and Their Effects on Dendritic Spine Density In Vivo.International journal of molecular sciences · 2023Article
- Therapeutic Potential of Targeting Regulated Intramembrane Proteolysis Mechanisms of Voltage-Gated Ion Channel Subunits and Cell Adhesion Molecules.Pharmacological reviews · 2022Review
- β-secretase inhibition prevents structural spine plasticity deficits inFrontiers in aging neuroscience · 2022Article
- The case for low-level BACE1 inhibition for the prevention of Alzheimer disease.Nature reviews. Neurology · 2021Review
- Functional Domains and Evolutionary History of the PMEL and GPNMB Family Proteins.Molecules (Basel, Switzerland) · 2021Article
- A Structure-Based Discovery Platform for BACE2 and the Development of Selective BACE Inhibitors.ACS chemical neuroscience · 2021Article
- Is It the Twilight of BACE1 Inhibitors?Current neuropharmacology · 2021Article
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- Functional Mammalian Amyloids and Amyloid-Like Proteins.Life (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Melanocytes of the hair follicle produce melanin and are essential in determining the differences in hair color. Pigment cell-specific MELanocyte Protein (PMEL17) plays a crucial role in melanogenesis. One of the critical steps is the amyloid-like functional oligomerization of PMEL17. Beta Site APP Cleaving Enzyme-2 (BACE2) and γ-secretase have been shown to be key players in generating the proteolytic fragments of PMEL17. The β-secretase (BACE1) is responsible for the generation of amyloid-β (Aβ) fragments in the brain and is therefore proposed as a therapeutic target for Alzheimer's disease (AD). Currently BACE1 inhibitors, most of which lack selectivity over BACE2, have demonstrated efficacious reduction of amyloid-β peptides in animals and the CSF of humans. BACE2 knock-out mice have a deficiency in PMEL17 proteolytic processing leading to impaired melanin storage and hair depigmentation. Here, we confirm BACE2-mediated inhibition of PMEL17 proteolytic processing in vitro in mouse and human melanocytes. Furthermore, we show that wildtype as well as bace2(+/-) and bace2(-/-) mice treated with a potent dual BACE1/BACE2 inhibitor NB-360 display dose-dependent appearance of irreversibly depigmented hair. Retinal pigmented epithelium showed no morphological changes. Our data demonstrates that BACE2 as well as additional BACE1 inhibition affects melanosome maturation and induces hair depigmentation in mice.
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