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Review
. 2022 Jan;35(1):6-17.
doi: 10.1111/pcmr.13006. Epub 2021 Aug 10.

The impaired unfolded protein-premelanosome protein and transient receptor potential channels-autophagy axes in apoptotic melanocytes in vitiligo

Bo Xie  1 , Xiuzu Song  1
Affiliations
Review

The impaired unfolded protein-premelanosome protein and transient receptor potential channels-autophagy axes in apoptotic melanocytes in vitiligo

Bo Xie et al. Pigment Cell Melanoma Res. 2022 Jan.

Abstract

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.

Keywords: autophagy; melanocyte; premelanosome protein; transient receptor potential channels; unfolded protein response; vitiligo.

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