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阐明黑色素生成级联反应，以鉴定色素性疾病和黑色素瘤的病理生理学和治疗方法。

Elucidation of Melanogenesis Cascade for Identifying Pathophysiology and Therapeutic Approach of Pigmentary Disorders and Melanoma.

机构信息

Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo 060-8543, Hokkaido, Japan.

Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

出版信息

Int J Mol Sci. 2020 Aug 25;21(17):6129. doi: 10.3390/ijms21176129.

DOI:10.3390/ijms21176129
PMID:32854423
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7503925/
Abstract

Melanogenesis is the biological and biochemical process of melanin and melanosome biosynthesis. Melanin is formed by enzymic reactions of tyrosinase family proteins that convert tyrosine to form brown-black eumelanin and yellow-red pheomelanin within melanosomal compartments in melanocytes, following the cascades of events interacting with a series of autocrine and paracrine signals. Fully melanized melanosomes are delivered to keratinocytes of the skin and hair. The symbiotic relation of a melanocyte and an associated pool of keratinocytes is called epidermal melanin unit (EMU). Microphthalmia-associated transcription factor (MITF) plays a vital role in melanocyte development and differentiation. MITF regulates expression of numerous pigmentation genes for promoting melanocyte differentiation, as well as fundamental genes for maintaining cell homeostasis. Diseases involving alterations of EMU show various forms of pigmentation phenotypes. This review introduces four major topics of melanogenesis cascade that include (1) melanocyte development and differentiation, (2) melanogenesis and intracellular trafficking for melanosome biosynthesis, (3) melanin pigmentation and pigment-type switching, and (4) development of a novel therapeutic approach for malignant melanoma by elucidation of melanogenesis cascade.

摘要

黑色素生成是黑色素和黑素小体生物合成的生物学和生化过程。黑色素是由酪氨酸酶家族蛋白的酶促反应形成的，这些蛋白将酪氨酸转化为棕色-黑色真黑色素和黄色-红色的褐黑素，在黑素细胞的黑素小体隔室中形成，沿着与一系列自分泌和旁分泌信号相互作用的级联事件进行。完全黑色素化的黑素小体被递送到皮肤和头发的角质细胞中。黑素细胞和相关的角质形成细胞池的共生关系称为表皮黑色素单位（EMU）。小眼畸形相关转录因子（MITF）在黑素细胞发育和分化中起着至关重要的作用。MITF 调节众多色素生成基因的表达，以促进黑素细胞分化，以及维持细胞内稳态的基本基因。涉及 EMU 改变的疾病表现出各种形式的色素沉着表型。本综述介绍了黑色素生成级联的四个主要主题，包括（1）黑素细胞的发育和分化，（2）黑色素生成和黑素小体生物合成的细胞内转运，（3）黑色素沉着和色素类型转换，以及（4）通过阐明黑色素生成级联阐明恶性黑色素瘤的新型治疗方法。

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