Gamma-secretase inhibitors down-regulate the pro-fibrotic Notch signaling pathway in recessive dystrophic epidermolysis bullosa

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare skin fragility disorder caused by mutations in COL7A1. RDEB is hallmarked by trauma-induced unremitting blistering, chronic wounds with inflammation and progressive fibrosis, leading to severe disease complications. There is currently no cure for RDEB-associated fibrosis. Our previous studies and increasing evidence highlighted the pro-fibrotic role of Notch pathway in different skin disorders, including RDEB. Here, we further investigated the role of Notch signaling in RDEB pathogenesis and explored the effects of its inhibition by γ-secretase inhibitors DAPT and PF-03084014 (nirogacestat).

Source: Journal of Investigative Dermatology - January 16, 2024 Category: Dermatology Authors: Angelo Giuseppe Condorelli, Rebecca Nobili, Anita Muglia, Giorgia Scarpelli, Elisa Marzuolo, Cristiano De Stefanis, Rossella Rota, Andrea Diociaiuti, Rita Alaggio, Daniele Castiglia, Teresa Odorisio, May El Hachem, Giovanna Zambruno Tags: Original Article Source Type: research