Xeroderma Pigmentosum (XP) is a rare genetic disease characterized by an enzymatic defect in the nucleotide excision repair (NER). Patients affected by XP show extreme sensitivity to sun exposure and high predisposition to develop skin tumors. In several studies, it was demonstrated that the bacterial DNA repair enzyme T4 endonuclease V (T4N5) can increase the rate of repair of DNA damage induced by ultraviolet light. The present thesis evaluated the activity of T4N5 liposome lotion in vitro model of dermal fibroblasts from healthy donors and patients affected by Xeroderma Pigmentosum. After exposure to UV radiation, in vitro model allowed the assessment of damage at the level of the cytoskeleton, the production of reactive oxygen species (ROS) and the analysis of mitochondrial activity. The results showed the restoration of some intracellular checkpoints (i.e. oxidative stress, inflammation, fibrosis and extracellular matrix integrity), preserving the structure and recovering cell metabolism in treated fibroblasts.

Enhanced Repair of UV-induced DNA damage by T4N5 liposomal lotion in Xeroderma Pigmentosum in vitro model

BRUNI, EMANUELA
2022/2023

Abstract

Xeroderma Pigmentosum (XP) is a rare genetic disease characterized by an enzymatic defect in the nucleotide excision repair (NER). Patients affected by XP show extreme sensitivity to sun exposure and high predisposition to develop skin tumors. In several studies, it was demonstrated that the bacterial DNA repair enzyme T4 endonuclease V (T4N5) can increase the rate of repair of DNA damage induced by ultraviolet light. The present thesis evaluated the activity of T4N5 liposome lotion in vitro model of dermal fibroblasts from healthy donors and patients affected by Xeroderma Pigmentosum. After exposure to UV radiation, in vitro model allowed the assessment of damage at the level of the cytoskeleton, the production of reactive oxygen species (ROS) and the analysis of mitochondrial activity. The results showed the restoration of some intracellular checkpoints (i.e. oxidative stress, inflammation, fibrosis and extracellular matrix integrity), preserving the structure and recovering cell metabolism in treated fibroblasts.
2022
Enhanced Repair of UV-induced DNA damage by T4N5 liposomal lotion in Xeroderma Pigmentosum in vitro model
Xeroderma
UV
DNA damage
Liposomes
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12608/48062