Vitiligo is an autoimmune skin disease, characterized by depigmentation and epidermal melanocytes loss. The specific mechanisms underlying vitiligo have not been fully understood. As a result, treating vitiligo is a dermatological challenge. Recently, much attention has been paid to the dysfunction and interaction of organelles under environmental stress. The impaired organelles could generate misfolded proteins, particularly accumulated toxic premelanosome protein (PMEL) amyloid oligomers, activating the autoimmune system and cause melanocyte damage. Unfolded protein response (UPR) dysfunction accelerates toxic PMEL accumulation. Herein, we presented a narrative review on UPR’s role in vitiligo, the misfolded PMEL-induced attack of the autoimmune system under autophagy dysfunction caused by abnormal activation of transient receptor potential (TRP) channels and the background of UPR system defects in melanocytes. All of these mechanisms were integrated to form UPR/PMEL-TRP channels/autophagy axis, providing a new understanding of vitiligo pathogenesis.

中文翻译：

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白癜风凋亡黑色素细胞中受损的未折叠蛋白-前黑素体蛋白和瞬时受体电位通道-自噬轴

白癜风是一种自身免疫性皮肤病，以脱色和表皮黑色素细胞丢失为特征。白癜风的具体机制尚未完全清楚。因此，治疗白癜风是一项皮肤病学挑战。近年来，环境胁迫下细胞器的功能障碍和相互作用引起了人们的广泛关注。受损的细胞器可能会产生错误折叠的蛋白质，特别是积累的有毒前黑素体蛋白 (PMEL) 淀粉样蛋白寡聚体，从而激活自身免疫系统并导致黑素细胞损伤。未折叠蛋白反应 (UPR) 功能障碍加速有毒 PMEL 积累。在此，我们对 UPR 在白癜风中的作用进行了叙述性回顾，在由瞬时受体电位（TRP）通道异常激活和黑素细胞中UPR系统缺陷的背景引起的自噬功能障碍下，错误折叠的PMEL诱导的自身免疫系统攻击。所有这些机制被整合形成UPR/PMEL-TRP通道/自噬轴，为白癜风发病机制提供了新的认识。