NRF2, a crucial modulator of skin cells protection against vitiligo, psoriasis, and cancer

Abstract

The skin represents a physical barrier between the organism and the environment that has evolved to confer protection against biological, chemical, and physical insults. The inner layer, known as dermis, is constituted by connective tissue and different types of immune cells whereas the outer layer, the epidermis, is composed by different layers of keratinocytes and an abundant number of melanocytes, localized in the stratum basale of the epidermis. Oxidative stress is a common alteration of inflammatory skin disorders such as vitiligo, dermatitis, or psoriasis but can also play a causal role in skin carcinogenesis and tumor progression. Nuclear factor (erythroid‐derived 2)‐like 2 (NRF2) has emerged as a crucial regulator of cell defense mechanisms activating complex transcriptional programs that facilitate reactive oxygen species detoxification, repair oxidative damage and prevent xenobiotic‐induced toxicity. Accumulating evidence suggests that the keratinocytes, melanocytes, and other skin cell types express high levels of NRF2, which is known to play a pivotal role in the skin homeostasis, differentiation, and metabolism during normal and pathologic conditions. In the present review, we summarize the current evidence linking NRF2 to skin pathophysiology and we discuss some recent modulators of NRF2 activity that have shown a therapeutic efficacy in skin protection against tumor initiation and common inflammatory skin conditions such as vitiligo or psoriasis, with a particular emphasis on natural compounds.

Sulforaphane alleviates psoriasis by enhancing antioxidant defense through KEAP1-NRF2 Pathway activation and attenuating inflammatory signaling

“…The KEAP1/NRF2 pathway demonstrates antioxidative and anti-in ammatory properties and plays a crucial role in maintaining skin homeostasis. Our study revealed that NRF2 is highly expressed in healthy skin, which aligns with ndings reported in public databases [37]. NRF2 activation emerges as a promising therapeutic approach for a range of skin disorders.…”

In vitro and in vivo evaluation of alginate hydrogel-based wound dressing loaded with green chemistry cerium oxide nanoparticles

“…In addition to its role as a shield, the skin performs several essential functions. It helps maintain moisture levels, enhances sensory perception, regulates body temperature, promotes the equilibrium of bodily fluids, and acts as a defense against foreign infections (Peate, 2021;Alalaiwe et al, 2023;Panieri et al, 2023). The skin possesses impressive adaptability, allowing it to withstand a range of environmental stressors over time.…”

Ex Vivo Analysis of Cell Differentiation, Oxidative Stress, Inflammation, and DNA Damage on Cutaneous Field Cancerization

“…These mutations disrupt normal cellular proliferation and facilitate escape from cell cycle control mechanisms [ 1 ]. Moreover, UV exposure amplifies the production of reactive oxygen species (ROS) through several pathways, notably those mediated by nuclear factor (erythroid-derived 2)-like 2 (NRF2) [ 38 , 39 ], NF-kB, and p63 [ 40 , 41 ]. Repeated UV exposure leads to additional cellular changes, causing cells to expand and displace normal tissue, ultimately contributing to the formation of AKs and cSCCs [ 42 ].…”