NRF2 in dermatological disorders: Pharmacological activation for protection against cutaneous photodamage and photodermatosis.
NRF2 in dermatological disorders: Pharmacological activation for protection against cutaneous photodamage and photodermatosis.
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DOI：
10.1016/j.freeradbiomed.2022.06.238
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发表时间：
2022-08-01
影响因子：
7.4
通讯作者：
Cohen, Guy
中科院分区：
文献类型：
--
作者：
Kahremany, Shirin;Hofmann, Lukas;Gruzman, Arie;Dinkova-Kostova, Albena T.;Cohen, Guy
关键词：
皮肤屏障及其内源性保护机制每天都要应对外源性压力源，其中紫外线辐射 (UVR) 构成迫在眉睫的危险。尽管皮肤能够减少潜在的损害，但仍需要采取全面的保护策略。这在开发预防光致癌的药理学方法时尤其重要。 NRF2 的激活有可能提供全面且持久的保护，因为许多细胞保护性下游效应蛋白的上调可以抵消 UVR 的破坏作用。这也适用于加剧紫外线损伤的光照性皮肤病。这篇综述描述了 UVR 在正常皮肤和光敏性疾病中引起的变化，并提供了支持 NRF2 激活剂作为药物治疗的开发的证据。总结了具有光保护特性的主要天然和合成活化剂。最后，强调了与光性皮肤病相关的研究知识的差距。总结了紫外线辐射的有害作用。紫外线引起的损伤在光敏感疾病中会加剧。 NRF2 的药理激活可以预防光损伤和光致癌。提出了靶向 NRF2 的局限性。
The skin barrier and its endogenous protective mechanisms cope daily with exogenous stressors, of which ultraviolet radiation (UVR) poses an imminent danger. Although the skin is able to reduce the potential damage, there is a need for comprehensive strategies for protection. This is particularly important when developing pharmacological approaches to protect against photocarcinogenesis. Activation of NRF2 has the potential to provide comprehensive and long-lasting protection due to the upregulation of numerous cytoprotective downstream effector proteins that can counteract the damaging effects of UVR. This is also applicable to photodermatosis conditions that exacerbate the damage caused by UVR. This review describes the alterations caused by UVR in normal skin and photosensitive disorders, and provides evidence to support the development of NRF2 activators as pharmacological treatments. Key natural and synthetic activators with photoprotective properties are summarized. Lastly, the gap in knowledge in research associated with photodermatosis conditions is highlighted. The deleterious action of ultraviolet radiation is summarized. UV-induced damage is aggravated in light sensitive disorders. Pharmacological activation of NRF2 can prevent photodamage and photocarcinogenesis. The limitations of targeting NRF2 is presented.
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