针对 ALDH1A1 治疗色素紊乱。
Targeting ALDH1A1 to treat pigmentary disorders.
机构信息
Department of Dermatology, University of Lübeck, Lübeck, Germany.
出版信息
Exp Dermatol. 2013 May;22(5):316-7. doi: 10.1111/exd.12134.
Clinical disorders related to skin pigmentation include hypo- or hyperpigmentation. Because they are difficult to treat, new approaches to develop safe pigment modulatory agents are needed. In the March issue of the journal, Paterson et al. (Exp Dermatol, 22, 2013) determined which aldehyde dehydrogenase 1A1 (ALDH1A1) substrates and products regulate melanogenesis. The authors demonstrated that ALDH1A1 substrate 9-cis retinal and its corresponding product 9-cis retinoic acid potently induced the accumulation of MITF mRNA, tyrosinase mRNA and melanin. Despite depletion of ALDH1A1, there was observed decreased ability of 9-cis retinal but not 9-cis retinoic acid to stimulate melanogenesis, indicating that ALDH1A1 regulates melanogenesis by catalysing the conversion of 9-cis retinal to 9-cis retinoic acid. Additionally, potent ALDH1A1 inhibitor such as cyanamide or Angeli's salt significantly suppressed pigmentation in human skin cells. These findings provide new candidate agents for the treatment of hypo- or hyperpigmentation disorders, using novel pigmentation-modulatory agents that target ALDH1A1.
与皮肤色素沉着相关的临床疾病包括色素减退或色素沉着过度。由于这些疾病难以治疗，因此需要开发新的方法来制备安全的色素调节药物。在该杂志 2013 年 3 月刊上，Paterson 等人（Exp Dermatol，22，2013）确定了哪些醛脱氢酶 1A1（ALDH1A1）的底物和产物可调节黑素生成。作者表明，ALDH1A1 底物 9-顺式视黄醛及其相应产物 9-顺式维甲酸可强烈诱导 MITFmRNA、酪氨酸酶 mRNA 和黑色素的积累。尽管 ALDH1A1 被耗尽，但观察到 9-顺式视黄醛而非 9-顺式维甲酸刺激黑素生成的能力下降，表明 ALDH1A1 通过催化 9-顺式视黄醛转化为 9-顺式维甲酸来调节黑素生成。此外，强效的 ALDH1A1 抑制剂如氰氨或安格利盐显著抑制了人皮肤细胞的色素沉着。这些发现为使用靶向 ALDH1A1 的新型色素调节药物治疗色素减退或色素沉着过度疾病提供了新的候选药物。
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