SKIN REDOX BALANCE MAINTENANCE: THE NEED FOR AN NRF2- ACTIVATORS DELIVERY SYSTEM

Maya Ben-Yehuda Greenwald, S. Sasson, H. Peled, R. Kohen
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Abstract

The skin, functions as a barrier between our body and the environment. Therefore, skin is consistently exposed to physical damages (e.g. wounds, sunburns) and to various exogenous and endogenous sources producing reactive oxygen species (e.g. air pollutants, ionizing and non-ionizing irradiation, toxins, mitochondrial metabolism, enzymes activity, etc.). Although skin has developed an array of counteracting defense mechanisms, augmented or continued reactive oxygen species activity may result in oxidative stress leading to many skin disorder including inflammatory diseases, pigmenting disorders and some types of cutaneous malignancies. The nuclear factor erythroid 2–related factor 2 (Nrf2) is an emerging regulator of cellular resistance and of defensive phase II enzymes. Induction of the Keap1-Nrf2 pathway may have a beneficial effect in treatment of a large number of skin disorders, by stimulating the endogenous defense mechanism. However, sustained and enhanced activation of this pathway is detrimental and limits the therapeutic potential of Keap1-Nrf2 activators. Here, we suggest a novel strategy for maintenance of skin redox homeostasis by modulating the Keap1-Nrf2 pathway using delivery systems.
皮肤氧化还原平衡维持:需要一个nrf2 -激活剂输送系统
皮肤是我们身体和环境之间的屏障。因此,皮肤持续暴露于物理损伤(如伤口、晒伤)和各种产生活性氧的外源性和内源性来源(如空气污染物、电离和非电离辐射、毒素、线粒体代谢、酶活性等)。尽管皮肤已经发展出一系列对抗防御机制,但活性氧活性的增强或持续可能导致氧化应激,导致许多皮肤疾病,包括炎症性疾病、色素沉着障碍和某些类型的皮肤恶性肿瘤。核因子红细胞2相关因子2 (Nrf2)是一种新兴的细胞抗性和防御性II期酶的调节因子。通过刺激内源性防御机制,诱导Keap1-Nrf2通路可能对治疗大量皮肤疾病具有有益作用。然而,该通路的持续和增强激活是有害的,并且限制了Keap1-Nrf2激活剂的治疗潜力。在这里,我们提出了一种通过使用递送系统调节Keap1-Nrf2通路来维持皮肤氧化还原稳态的新策略。
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