{
    "abstract": "Melanin in skin and hair protects cells from UV damage; however, uneven skin color or hyperpigmentation is a common aesthetic concern. Melanin is synthesized in melanosomes, organelles within melanocytes, where tyrosinase converts tyrosine to melanin. Trafficking of tyrosinase or other cargo (eg, premelanosome protein [PMEL]) may depend on vesicle-associated membrane proteins (VAMPs); interfering with VAMPs has been reported to impact melanogenesis. Botulinum neurotoxin type DC (BoNT/DC) is a naturally occurring mosaic serotype that cleaves SNARE proteins VAMP1-3. This study evaluated BoNT/DC as a potential treatment for hyperpigmentation by testing if it affects melanogenesis. In melanocytes BoNT/DC cleaved VAMP2 and VAMP3, and knockdown of VAMP3, but not VAMP2, reduced melanin content, which suggests that BoNT/DC may affect melanogenesis via VAMP3 cleavage. Indeed, BoNT/DC (5 nM) produced a \u223c50% reduction in melanin content in melanocytes, and in 2 human melanocyte models, BoNT/DC, but not BoNT/A, significantly reduced melanin content (\u223c40-50%) without cytotoxicity. Electron microscopy showed that BoNT/DC-treated melanocytes contained more early-stage (II) and fewer late-stage (IV) melanosomes than vehicle- or BoNT/A-treated melanocytes. Overall, BoNT/DC reduced melanin content in multiple melanocyte models, and its lightening effects are likely due to VAMP3 cleavage interfering with trafficking of cargo (eg, tyrosinase, PMEL) required for melanogenesis.",
    "authors": [
        {
            "affiliation": "Allergan Aesthetics, an AbbVie company, 2525 Dupont Drive, Irvine, CA, 92612, USA.",
            "firstname": "Shiazah",
            "initials": "S",
            "lastname": "Malik"
        },
        {
            "affiliation": "Allergan Aesthetics, an AbbVie company, 2525 Dupont Drive, Irvine, CA, 92612, USA.",
            "firstname": "Linh",
            "initials": "L",
            "lastname": "Le"
        },
        {
            "affiliation": "Department of Dermatology, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45229, USA.",
            "firstname": "Raymond E",
            "initials": "RE",
            "lastname": "Boissy"
        },
        {
            "affiliation": "Allergan Aesthetics, an AbbVie company, 2525 Dupont Drive, Irvine, CA, 92612, USA.",
            "firstname": "Amy",
            "initials": "A",
            "lastname": "Brideau-Andersen"
        },
        {
            "affiliation": "Allergan Aesthetics, an AbbVie company, 2525 Dupont Drive, Irvine, CA, 92612, USA. Electronic address: birgitte.sondergaard@abbvie.com.",
            "firstname": "Birgitte",
            "initials": "B",
            "lastname": "Sondergaard"
        }
    ],
    "conclusions": null,
    "copyrights": "Copyright \u00a9 2025. Published by Elsevier Ltd.",
    "doi": "10.1016/j.toxicon.2025.108372",
    "journal": "Toxicon : official journal of the International Society on Toxinology",
    "keywords": [
        "botulinum neurotoxin",
        "hyperpigmentation",
        "melasma",
        "skin quality"
    ],
    "methods": null,
    "publication_date": "2025-04-27",
    "pubmed_id": "40286827",
    "results": null,
    "title": "Botulinum neurotoxin type DC (BoNT/DC) cleavage of VAMP3 reduces melanin production in melanocytes.",
    "xml": "<Element 'PubmedArticle' at 0x788503fdec50>"
}