Plerixafor Engages β-Arrestin-Dependent CXCR4 Signaling to Promote Melanogenesis via β-Catenin-MITF Activation

The study explores the effects of Plerixafor, a CXCR4 antagonist, on melanogenesis and pigmentation. It shows that Plerixafor enhances the expression of melanogenic genes MITF and tyrosinase, promotes melanocyte migration, and counteracts hydroquinone-induced gene suppression through β-arrestin-dependent signaling. In a murine model, Plerixafor restored depigmentation, increased hair follicle number and melanin content, and showed no systemic toxicity. These findings suggest Plerixafor as a potential therapeutic agent for re-pigmentation in pigmentary disorders, with its effects confirmed through at least 5 independent experiments and involving 5 mice per group in vivo.